Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1

专利摘要:
The present invention relates to a compound having the formula (II) and also a pharmaceutical composition comprising the compound, a process for their preparation and the use of the compound in medicine, as well as a pharmaceutical agent that acts on human 11-β-hydroxysteroid dehydrogenase type 1 enzyme It relates to a manufacturing process.
公开号:KR20030016269A
申请号:KR1020027015703
申请日:2001-05-22
公开日:2003-02-26
发明作者:바르프티져드；에몬드리카르드；쿠르츠구이도；발가르다져크；닐쓴마리안
申请人:바이오비트럼 에이비；
IPC主号:

专利说明:

INHIBITORS OF 11-BETA-HYDROXY STEROID DEHYDROGENASE TYPE 1} Inhibitor of 11-beta-hydroxy steroid dehydrogenase type 1
[2] 1. Preparation of Glucocorticoids, Diabetes and Hepatic Glucose
[3] For more than half a century, glucocorticoids play a central role in diabetes, for example, the removal of the pituitary gland or adrenal glands from diabetic animals has been known to alleviate the most severe symptoms of diabetes and lower blood glucose levels (Long, CD and FDW Leukins (1936) J. Exp. Med. 63: 465490; Houssay, BA (1942) Endocrinology 30: 884-892). It is also well documented that glucocorticoids enable the effects of glucagon in the liver.
[4] The local glucocorticoid effect and therefore the role of 11βHSD1 as an important regulator of hepatic glucose production is well specified (see, for example, Jamieson et al. (2000) J. Endocrinol. 165: p. 685-692.) Hepatic insulin sensitivity. Was improved in healthy volunteers treated with the nonspecific 11βHSD1 inhibitor carbenoxolone (Walker, BR et al. (1995) J. Clin. Endocrinol. Metab. 80: 3155-3159). In addition, the expected mechanism was confirmed by other experiments with mice and rats. These studies show two major enzymes in hepatic glucose production: rate-limiting enzymes in the neosynthesis of glucose, phosphoenolpyruvate carboxykinase (PEPCK) and the last common generalization of glucose's neosynthesis and glycogenolysis. It has been shown that the mRNA level and activity of glucose-6 phosphatase (G6Pase), which promotes the stage, has been reduced. Finally, blood glucose levels and hepatic glucose production are reduced in mice with the knockout 11βHSD1 gene. Data from this model also confirms that inhibition of 11βHSD1 will not cause hypoglycemia, as predicted that basal levels of PEPCK and G6Pase are independently regulated by glucocorticoids (Kotelevtsev, Y. et al., (1997). Proc. Natl. Acad. Sci. USA 94: 14924-14929).
[5] 2. Reduction of possible obesity and obesity related cardiovascular risk factors
[6] Obesity is an important factor in syndrome X as well as most (> 80%) type 2 diabetes, and long-term fat appears to be of central importance. Abdominal obesity is closely related to endogenous disorders, hyperinsulinemia, hypertriglyceridemia, and other factors of so-called syndrome X (e.g. elevated blood pressure, reduced levels of HDL and increased levels of VLDL) Montague & O'Rahilly, Diabetes 49: 883-888,2000). Inhibition of enzymes in precursor adipocytes (stromal cells) has been shown to reduce the rate of differentiation into adipocytes. This is expected to result in a reduced expansion (possibly a reduction) of long-term fat stores, i.e., reduced centrality ratios (Bujalska, I. J., S. Kumar, and P. M. Stewart (1997) Lancet 349: 1210-1213).
[7] Inhibition of 11βHSD1 in mature adipocytes is expected to attenuate the secretion-independent cardiovascular risk factors of plasminogen activator inhibitor 1 (PAI-1) (Halleux, CM et al. (1999) J. Clin. Endocrinol. Metab. 84: 4097-4105). In addition, there is a clear correlation between glucocorticoid “activity” and cardiovascular risk factors, suggesting that a reduction in glucocorticoid effect would be beneficial (Walker, BR et al. (1998) Hypertension 31: 891-895; Fraser, R et al. (1999) Hypertension 33: 1364-1368).
[8] Adrenal ablation attenuates the effect of fasting to increase both food intake and hypothalamic neuropeptide Y expression. This supports the role of glucocorticoids in promoting food intake, suggesting that inhibition of 11βHSD1 in the brain increases satiety and thus reduces food intake (Woods, SC et al. (1998) Science, 280: 1378-1383). .
[9] 3. Possible beneficial effects on the pancreas
[10] Inhibition of 11βHSD1 in isolated murine pancreatic β-cells improves glucose-stimulated insulin secretion (Davani, B. et al. (2000) J. Biol. Chem. 2000 Nov 10; 275 (45): 34841-4 ). Glucocorticoids were previously known to reduce pancreatic insulin release in vivo (Billaudel, B. and B. C. J. Sutter (1979) Horm. Metab. Res. 11: 555-560). Thus, inhibition of 11βHSD1 is expected to have other beneficial effects for the treatment of diabetes, in addition to effects on liver and fat.
[11] 4. Possible beneficial effects on cognition and dementia
[12] Stress and glucocorticoids affect cognitive function (de Quervain, D. J.-F., B. Roozendaal, and J. L. McGaugh (1998) Nature 394: 787-790). The enzyme 11βHSD1 controls the level of glucocorticoid action in the brain and thus contributes to neurotoxicity (Rajan, V., CRW Edwards, and JR Seckl, J. (1996) Neuroscience 16: 65-70; Seckl, JR, Front. (2000) Neuroendocrinol. 18: 49-99). Unpopulated results show significant memory improvement in rats treated with nonspecific 11βHSD1 inhibitors (J. Seckl, personal communication). Based on the above and the known effects of glucocorticoids in the brain, it can also be suggested that inhibiting 11βHSD1 in the brain can reduce anxiety (Tronche, F. et al. (1999) Nature Genetics 23: 99- 103). Thus, taken together, the hypothesis suggests that inhibition of 11βHSD1 in the human brain prevents reactivation of cortisone to cortisol and is directed to other aspects of neuronal function, including neuronal survival and cognitive impairment, depression and increased appetite (previous section). To protect against toxic glucocorticoid-mediated effects.
[13] 5. Possible Use of Immune-Regulatory Using 11βHSD1 Inhibitor
[14] A common perception is that glucocorticoids suppress the immune system. In fact, however, there is a dynamic interaction between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis (Rook, G. A. W. (1999) Bailler's Clin. Endocrinol. Metab. 13: 576-581). The balance between cell-mediated and humoral responses is regulated by glucocorticoids. High glucocorticoid activity, such as in a state of stress, is associated with humoral responses. Thus, inhibition of the enzyme 11βHSD1 has been proposed as a means of shifting the response towards a cell-based response.
[15] In certain disease states, including tuberculosis, leprosy, and psoriasis, immune action is normally biased towards the humoral response when the proper response is cell based. Local or tissue transient inhibition of 11βHSD1 will be used to propel the immune system to appropriate responses (Mason, D. (1991) Immunology Today 12: 57-60; Rook et al., Supra).
[16] In this case, a similar use of transient, 11βHSD1 inhibition will promote the immune response associated with immunization, ensuring that cell-based responses are obtained when desired.
[17] 6.Reduction of intraocular pressure
[18] Recent data suggest that levels of glucocorticoid target receptor and 11βHSD enzyme determine susceptibility to glaucoma (Stokes, J. et al. (2000) Invest. Ophthalmol. 41: 1629-1638). In addition, 11βHSD1 inhibition has recently emerged as a novel approach to lower intraocular pressure (Walker E. A. et al, poster P3-698 at the Endocrine society meeting June 12-15,1999, San Diego). Ingestion of carbenoxolone, a nonspecific inhibitor of 11βHSD1, has been shown to reduce intraocular pressure by 20% in normal subjects. In the eye, the expression of 11βHSD1 is limited to the corneal epithelium and basal cells of the uncolored epithelium of the cornea (site of water production), ciliary muscle and sphincter and dilatation muscle of the iris. In contrast, priming enzyme 11βHSD2 is highly expressed in uncolored ciliary epithelium and corneal endothelium. No enzyme is found in the trabecular meshwork, the site of drainage. Thus, 11βHSD1 is suggested to play a role in aqueous preparation, rather than fold, but at present it is not known if this interferes with the activity of glucocorticoid or mineralocorticoid receptors, or both.
[19] 7.Reduced Osteoporosis
[20] Glucocorticoids play an essential role in skeletal development and function, but are excessively harmful. Glucocorticoid-induced bone loss is induced, at least in part, through inhibition of bone formation, which includes inhibition of osteoblast proliferation and collagen synthesis (Kim, CH, SL Cheng, and GS Kim (1999) J. Endocrinol. 162: 371-379). Negative effects on fracture formation could be blocked by nonspecific inhibitor carbenoxolone, suggesting an important role of 11βHSD1 (Bellows, C. G., A. Ciaccia, and J. N. M. Heersche, (1998) Bone 23: 119-125). Other data suggest that the role of 11βHSD1 provides sufficiently high levels of active glucocorticoids in osteoclasts, thus increasing bone resorption (Cooper, M. S. et al. (2000) Bone 27: 375-381). Taken together, these other dieters suggest that inhibition of 11βHSD1 may have a beneficial effect on osteoporosis by one or more mechanisms working in parallel.
[21] WO 99/65884 discloses carbon substituted aminothiazole inhibitors of cyclin dependent kinases. These compounds can be used for example for cancer, inflammation and arthritis. US 5,856,347 discloses antimicrobial preparations or bactericides comprising 2-aminothiazole derivatives and / or salts thereof. In addition, US 5,403,857 discloses benzenesulfonamide derivatives having 5-lipoxygenase inhibitory activity. Additionally, tetrahydrothiazolo [5, 4-c] pyridine is: analgesic tetrahydrothiazolo [5,4-c] pyridine. Fr. Addn. (1969), 18 pp, Addn. to Fr. 1498465. CODEN: FAXXA3; FR 94123 19690704 CAN 72: 100685 AN 1970: 100685 CAPLUS and 4, 5, 6, 7-tetrahydrothiazolo [5, 4-c] pyridine. Neth. Appl. (1967), 39 pp. CODEN: NAXXAN NL 6610324 19670124 CAN 68: 49593, AN 1968: 49593 CAPLUS.
[22] However, none of the above disclosures disclose the compounds according to the invention, but their use for the treatment of diabetes, obesity, glaucoma, osteoporosis, cognitive disorders, immune disorders and depression.
[23] As a result, there is a need for new compounds useful for the treatment of diabetes, obesity, glaucoma, osteoporosis, cognitive impairment, immune disorders and depression.
[1] The present invention provides for the preparation of medicaments that act on human 11-β-hydroxysteroid dehydrogenase type 1 enzyme (11βHSD1) as well as novel compounds, pharmaceutical compositions comprising the compounds, their preparation processes and the use of the compounds in medicine. It is about process.
[24] Disclosure of the Invention
[25] The compounds according to the present invention solve the above problems, have been developed and inhibit the human 1l-β-hydroxysteroid dehydrogenase type 1 enzyme (1l-β-HSDl) and thus diabetes, obesity, glaucoma, osteoporosis, cognitive impairment And new classes of compounds that can be used in the treatment of disorders such as immune disorders and depression.
[26] One object of the invention is to formula II
[27]
[28] Or a salt, hydrate or solvate thereof.
[29] Wherein T is an aryl ring or heteroaryl ring or aryl-C ₂ -alkenyl ring, optionally independently substituted by [R] n, where n is an integer 0-5 and R is hydrogen, aryl, hetero Aryl, heterocyclic ring, optionally halogenated C _1-6 -alkyl, optionally halogenated C _1-6 -alkoxy, C _1-6 -alkylsulfonyl, carboxy, cyano, nitro, halogen, optionally mono- Or di-substituted amines, optionally mono- or di-substituted amides, aryloxy, arylsulfonyl, arylamino, wherein the aryl, heteroaryl and aryloxy moieties and heterocyclic rings are more optionally at one or more positions independently of each other C _1-6 - acylamino, C _1-6 - alkylthio, cyano, nitro, hydrogen, halogen, optionally halogenated C _l-6-alkyl, optionally halogenated C _1-6 - alkoxy, optionally Mono- or di-substituted amides with (benzoylamino ) Methyl, carboxy, 2-thienylmethylamino or ({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) have ;
[30] Provided that when R ¹ is H, X is CH ₂ , Y is CO, R ² is EtO and B is H, then T is 2,4-dichloro-5-methylphenyl, 4-chlorophenyl, 4-chloro -2,5-dimethylphenyl, 2,4-difluorophenyl, 3-nitrophenyl and phenyl;
[31] Optionally also when R ¹ is H, X is CH ₂ , Y is CO, R ² is OH and B is H, then T is not 4-aminophenyl; Optionally also
[32] When R ¹ is H, X is CH ₂ , Y is CO, R ² is MeO and B is H, then T is not 4-acetylaminophenyl;
[33] R ¹ is hydrogen or C _1-6 -alkyl;
[34] X is CH ₂ or CO;
[35] Y is CH ₂ , CO or a single bond;
[36] B is hydrogen, C _1-6 -alkyl or dimethylaminomethyl;
[37] R ² is C _1-6 -alkyl, azido, arylthio, heteroarylthio, halogen, hydroxymethyl, 2-hydroxyethylaminomethyl, methylsulfonyloxymethyl, 3-oxo-4-morpholinolinyl Methylene, C _1-6 -alkoxycarbonyl, 5-methyl-1,3,4-oxadiazol-2-yl;
[38] NR ³ R ⁴ , wherein R ³ and R ⁴ are each independently hydrogen, C _1-6 -alkyl, optionally halogenated C _1-6 -alkylsulfonyl, C _1-6 -alkoxy, 2-methoxyethyl, 2 -Hydroxyethyl, 1-methylimidazolylsulfonyl, C _1-6 -acyl, cyclohexylmethyl, cyclopropanecarbonyl, aryl, optionally halogenated arylsulfonyl, furylcarbonyl, tetrahydro-2-furanyl Methyl, N-carbetoxypiperidyl, or C _1-6 -alkyl substituted with one or more aryl or heteroaryl, or
[39] NR ³ R ⁴ is amidazole, piperidine, pyrrolidine, piperazine, morpholine, oxazepine, oxazole, thiomorpholine, 1,1-dioxidothiomorpholine, 2- (3,4- Dihydro-2 (1H) isoquinolinyl), (1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept-5-yl, together with Heterocyclic systems may be optionally substituted by C _1-6 -alkyl, C _1-6 -acyl, hydroxy, oxo, t-butoxycarbonyl;
[40] OCONR ³ R ⁴ , wherein R ³ and R ⁴ are each independently selected from hydrogen, C _1-6 -alkyl or together form morpholinyl;
[41] R ⁵ 0, wherein R ⁵ is hydrogen, optionally halogenated C _1-6 -alkyl, aryl, heteroaryl, C _1-6 -acyl, C _1-6 -alkylsulfonyl, arylcarbonyl, heteroarylcarbonyl, 2-carbomethoxyphenyl; )
[42] It is preferred that:
[43] T is 5-chloro-1,3-dimethyl-lH-pyrazol-4-yl; 4-chloro-2,3,1 benzoxadiazolyl; 5- (dimethylamino) -1-naphthyl; 1-methylimidazol-4-yl; 1-naphthyl;
[44] 2-naphthyl; (E) -2-phenylethenyl; 8-quinolinyl;
[45] (Benzoylamino) methyl, bromo, chloro, 3-isoxazolyl, 2- (methylsulfanyl) -4-pyrimidinyl, 1-methyl-5- (trifluoromethyl) pyrazol-3-yl, Thienyl substituted with one or more of phenylsulfonyl, pyridyl;
[46] Acetylamino, 3-acetylaminophenyl, 3-acetylphenyl, benzeneamino, 1,3-benzodioxol-5-yl, 2-benzofuryl, benzylamino, 3,5-bis (trifluoromethyl) phenyl, Bromo, butoxy, carboxy, chloro, 4-carboxyphenyl, 3-chloro-2-cyanophenoxy, 4-chlorophenyl, 5-chloro-2-thienyl, cyano, 3,4-dichlorophenyl, ({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl), fluoro, 5-fluoro-2-methoxyphenyl, 2- Furyl, hydrogen, iodo, isopropyl, methanesulfonyl, methoxy, methyl, 4-methyl-l-piperazinyl, 4-methyl-l-piperidinyl, 4-methylsulfanylphenyl, 5-methyl- 2-thienyl, 4-morpholinyl, nitro, 3-nitrophenyl, phenoxy, phenyl, n-propyl, 4-pyridyl, 3-pyridylmethylamino, 1-pyrrolidinyl, 2-thienyl, Substituted with one or more of 3-thienyl, 2-thienylmethylamino, trifluoromethoxy, 4-trifluoromethoxyphenyl, trifluoromethyl Selected from phenyl or; or
[47] Provided that when R ¹ is H, X is CH ₂ , Y is CO, R ² is EtO and B is H, then T is 2,4-dichloro-5-methylphenyl, 4-chlorophenyl, 4-chloro -2,5-dimethylphenyl, 2,4-difluorophenyl, 3-nitrophenyl and phenyl;
[48] Optionally also when R ¹ is H, X is CH ₂ , Y is CO, R ² is OH and B is H, then T is 4-aminophenyl; Optionally also
[49] When R ¹ is H, X is CH ₂ , Y is CO, R is MeO and B is H, then T is not 4-acetylaminophenyl;
[50] R ¹ is hydrogen or methyl;
[51] X is CH ₂ or CO;
[52] Y is CH ₂ , CO or a single bond;
[53] B is hydrogen, methyl or dimethylaminomethyl;
[54] R ² is n-propyl, azido, bromo, chloro, 2-pyridinylsulfanyl, 3-oxo-4-morpholinolinyl methylene, ethoxycarbonyl, 5-methyl-1,3,4-oxa Diazol-2-yl, hydroxymethyl, 2-hydroxyethylaminomethyl, methylsulfonyloxymethyl;
[55] NR ³ R ⁴ , wherein R ³ and R ⁴ are each independently acetyl, benzhydryl, 1,3-benzodioxol-5-ylmethyl, benzyl, 3-chloro-2-methylphenylsulfonyl, cyclohexyl, cyclo Hexylmethyl, cyclopropanecarbonyl, ethyl, 2-furylcarbonyl, 2-furylmethyl, hydrogen, 2-hydroxyethyl, 2- (lH-indol-3-yl) ethyl, isopropyl, methoxy, 2- Methoxyethyl, methyl, 4- (1-methylimidazolyl) sulfonyl, methylsulfonyl, phenyl, (1S) -phenylethyl, n-propyl, tetrahydro-2-furanylmethyl, trifluoromethylsul Fonyl, N-carbetoxypiperidyl; or
[56] NR ³ R ⁴ together is 4-acetylpiperazinyl, 4-t-butoxycarbonylpiperazinyl, 2- (3, 4-dihydro-2 (1H) isoquinolinyl); (2R, 6S) -2, 6-dimethylmorpholinyl, (2R) -2,4-dimethyl-1-piperazinyl, 2-hydroxy-3-oxomorpholinyl, imidazolyl, 2-methyl -3-oxomorpholinyl, 4-methyl-2-oxopiperazinyl, 4-methylpiperazinyl, morpholinyl, (1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept -5-yl, 2-oxoimidazolinyl, 3-oxomorpholinyl, 3-oxo-1, 4-oxazinyl, 2-oxooxazolinyl, piperazinyl; Piperidinyl; Pyrrolidinyl; Pyrrolidoneyl, thiomorpholinyl; 1, 1-dioxido-thiomorpholinyl;
[57] OCONR ³ R ⁴ , wherein R ³ and R ⁴ are each independently selected from ethyl, hydrogen or together form morpholinyl; R ⁵ 0, where R ⁵ is acetyl, benzoyl, benzyl, ethyl, 2-fluoroethyl, 2-furylcarbonyl, hydrogen, isobutyryl, isopropyl, methyl, 2-carbomethoxyphenyl, methylsulfonyl, Phenyl, propionyl, 3-pyridinyl, 2,2,2-trifluoroethyl.
[58] When T is a substituted phenyl group, the phenyl ring is preferably substituted as follows:
[59] a) T is phenyl, wherein phenyl is one or more acetylamino, 3-acetylaminophenyl, 3-acetylphenyl, benzeneamino, 2-benzofuryl, benzylamino, 3, 5-bis (trifluoromethyl) phenyl, Bromo, butoxy, carboxy, 4 carboxyphenyl, 3-chloro-2-cyanophenoxy, 4-chlorophenyl, 5-chloro-2-thienyl, cyano, 3,4-dichlorophenyl, ({[ 4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl), 5-fluoro-2-methoxyphenyl, 2-furyl, iodo, iso Propyl, methanesulfonyl, methoxy, methyl, 3,4-methylenedioxyphenyl, 4-methyl-1- piperazinyl, 4-methyl-1 -piperidinyl, 4-methylsulfanylphenyl, 5-methyl 2-thienyl, 4-morpholinyl, 3-nitrophenyl, phenoxy, phenyl, n-propyl, 4-pyridyl, 3-pyridylmethylamino, 1-pyrrolidinyl, 2-thienyl, 3- Substituted with thienyl, 2-thienylmethylamino, trifluoromethoxy, 4-trifluoromethoxyphenyl, trifluoromethyl All;
[60] b) T is substituted with chloro at one or more positions 3,5, or 6 and one or more acetylamino, 3-acetylaminophenyl, 3-acetylphenyl, benzeneamino, 2-benzofuryl, benzylamino, 3,5-bis (Trifluoromethyl) phenyl, bromo, butoxy, carboxy, 4-carboxyphenyl, 3-chloro-2-cyanophenoxy, 4-chlorophenyl, 5-chloro-2 thienyl, cyano, 3, 4-dichlorophenyl, ({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl), 5-fluoro-2-methoxyphenyl, 2-furyl, iodo, isopropyl, methanesulfonyl, methoxy, methyl, 3,4-methylenedioxyphenyl, 4-methyl-1-piperazinyl, 4-methyl-l-piperidinyl, 4- Methylsulfanylphenyl, 5-methyl-2-thienyl, 4-morpholinyl, 3-nitrophenyl, phenoxy, phenyl, n-propyl, 4-pyridyl, 3 pyridylmethylamino, 1-pyrrolidinyl , 2-thienyl, 3-thienyl, 2-thienylmethylamino, trifluoromethoxy, 4-trifluoromethoxyphenyl, tetra It is replaced by a fluoromethyl; or
[61] c) T is chloro at position 2 and at least one acetylamino, 3-acetylaminophenyl, 3-acetylphenyl, benzeneamino, 2-benzofuryl, benzylamino, 3,5-bis (trifluoromethyl) phenyl, Bromo, butoxy, carboxy, 4 carboxyphenyl, 3-chloro-2-cyanophenoxy, 4-chlorophenyl, 5-chloro-2-thienyl, cyano, 3,4-dichlorophenyl, ({[ 4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl), 5-fluoro-2-methoxyphenyl, 2-furyl, iodo, iso Propyl, methanesulfonyl, methoxy, methyl, 3,4-methylenedioxyphenyl, 4-methyl-1 piperazinyl, 4-methyl-1 -piperidinyl, 4-methylsulfanylphenyl, 5-methyl- 2-thienyl, 4-morpholinyl, 3-nitrophenyl, phenoxy, phenyl, n-propyl, 4-pyridyl, 3-pyridylmethylamino, 1-pyrrolidinyl, 2-thienyl, 3-thieryl To ethyl, 2-thienylmethylamino, trifluoromethoxy, 4-trifluoromethoxyphenyl, trifluoromethyl Hwandoen is phenyl; or
[62] d) T is phenyl substituted with one or three fluorine and optionally with one or more bromo and methyl.
[63] The following compounds are particularly preferred:
[64] Ethyl 2- (2-(((4-methylphenyl) sulfonyl) amino) -1,3-thiazol-4-yl) acetate,
[65] Ethyl 2- (2-{[(2, 5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[66] Ethyl (2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[67] Ethyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[68] Ethyl 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl) acetate,
[69] Ethyl 2- (2-{[(3-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[70] Ethyl (2-{[(4-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[71] Ethyl (2-{[(4-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[72] Ethyl (2-{[(3-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[73] Ethyl (2-{[(3-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[74] Ethyl (2-{[(4-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[75] Ethyl (2-{[(3-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[76] Ethyl (2-{[(4-isopropylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[77] Ethyl [2-({[3-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino)- 1,3-thiazol-4-yl] acetate,
[78] Ethyl [2-({[4-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino)- 1,3-thiazol-4-yl] acetate,
[79] Ethyl (2-{[(2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[80] Ethyl [2-({[2- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[81] Ethyl [2-({[3- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[82] Ethyl [2-({[4- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[83] Ethyl 2- (2-{[(4-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[84] Ethyl (2-{[(2-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[85] Ethyl (2-{[(2, 4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[86] Ethyl (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[87] Ethyl (2-{[(2,4-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[88] Ethyl (2-{[(5-fluoro-2-methylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) acetate,
[89] Ethyl (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[90] Ethyl (2-{[(2-methoxy-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[91] Ethyl (2-{[(3,5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[92] Ethyl [2-({[4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[93] Ethyl (2-{[(3,4-dichlorophenyl) sulfonyl amino} -1,3-thiazol-4-yl) acetate,
[94] Ethyl (2-([(4-butoxyphenyl) sulfonyl] amino] -1,3-thiazol-4-yl) acetate,
[95] Ethyl (2- [(4-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[96] Ethyl [2- ({[4- (acetylamino) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[97] Ethyl {2-[(8-quinolinylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
[98] Ethyl (2-{[(3,4-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[99] Ethyl (2-{[(4-iodophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[100] Ethyl (2-{[(3-chloro-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[101] Ethyl [2-({5- (dimethylamino) -1-naphthyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[102] Ethyl (2-{[(1-methyl-1H-imidazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[103] Ethyl (2-{[(5-bromo-2-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[104] Ethyl (2-{[(2,5-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[105] Ethyl {2-[(2-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
[106] Ethyl {2-[(methylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
[107] Ethyl (2-{[(3-bromo-5-chloro-2-thienyl) sulfonyl] amino] -1,3-thiazol-4-yl) acetate,
[108] Ethyl {2-[(5-[(benzoylamino) methyl] -2-thienyl} sulfonyl) amino] -1,3-thiazol-4-yl} acetate,
[109] Ethyl {2-[({5- [l-methyl-5- (trifluoromethyl) -lH-pyrazol-3-yl] -2- thienyl} sulfonyl) amino] -1,3-thiazole -4-yl} acetate,
[110] Ethyl (2-{[(4-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[111] Ethyl {2-[({5- [2- (methylsulfanyl) -4-pyrimidinyl] -2-thienyl} sulfonyl) amino] -1,3 thiazol-4-yl} acetate,
[112] Ethyl (2-{[(3-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[113] Ethyl (2-{[(2,4,5-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[114] Ethyl [2 [{[(((E) -2-phenylethenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[115] Ethyl (2-{[(2,3,4-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[116] Ethyl (2-{[(4-bromo-2, 5-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[117] Ethyl [2-({[4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[118] Ethyl (2-{[(2, 3-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[119] Ethyl (2-{[(2-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[120] Ethyl (2-{[(4,5-dichloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[121] Ethyl [2-({[4- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[122] Ethyl [2-{[(5- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[123] Ethyl (2-{[(2, 6-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[124] Ethyl (2-{[(2-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[125] Ethyl [2-({[4- (acetylamino) -3-chlorophenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[126] Ethyl (2-{[(5-chloro-1,3-dimethyl-lH-pyrazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[127] Ethyl (2-{[(3-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[128] Ethyl (2- {[(4-bromo-5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[129] Ethyl 2- {2-[(l-naphthylsulfonyl) amino] -1, 3-thiazol-4-yl} acetate,
[130] Ethyl (2-{[(2, 5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[131] Ethyl [2- {[(4- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[132] Ethyl [2-{[(2- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[133] Ethyl (2-{[(4-bromo-2-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[134] Ethyl (2-{[(2,3,4-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[135] Ethyl (2-{[(7-chloro-2,1,3-benzoxadiazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[136] Ethyl (2-{[(2,4,6-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[137] 2-chloro-5-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} sulfonyl) -4-fluorobenzoic acid,
[138] Ethyl (2-{[(5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[139] Ethyl (2-{[(2-chloro-4-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[140] Ethyl [2-({[5- (3-isoxazolyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[141] Ethyl (2-{[(4-bromo-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[142] Ethyl (2-{[(4-phenoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[143] Ethyl (2-{[(4-chloro-2, 6-dimethylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[144] Ethyl [2-{[(2-methyl-4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[145] Ethyl [2-({[2,4-bis (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[146] Ethyl 2- [2-{[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] -1,3-thiazol-4-yl} acetate,
[147] Ethyl oxo (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[148] Ethyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) (oxo) acetate,
[149] Ethyl oxo (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[150] Ethyl [2-{[(1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} (oxo) acetate,
[151] Ethyl (2-{[(2, 4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) (oxo) acetate,
[152] 2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
[153] 2- (2- {[(2, 5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
[154] (2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
[155] 2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3 thiazol-4-yl) acetic acid,
[156] Isopropyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[157] Phenyl 2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[158] Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[159] Methyl {2-[([l, 1'-biphenyl] -4-ylsulfonyl) amino] -5-methyl-1,3-thiazol-4-yl} acetate,
[160] Methyl (2-{[(4-chlorophenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
[161] Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
[162] Methyl [2- {[(4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -5-methyl-1,3-thiazol-4-yl] acetate,
[163] Methyl (5-methyl-2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[164] Methyl (5-methyl-2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[165] Methyl (2-{[((2,4-dichloro-6-methylphenyl) sulfonyl] amino} -5-methyl-1, 3-thiazol-4-yl) acetate,
[166] N- (2-methoxyethyl) -2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[167] 2- (2-{[(2,5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
[168] N- (1,3-benzodioxol-5-ylmethyl) -2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
[169] N- (2-furylmethyl) -2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
[170] 2- (2-{[(2,4-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
[171] N-isopropyl-2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
[172] N- [2- (lH-indol-3-yl) ethyl] -2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
[173] N- (cyclohexylmethyl) -2- {2-[(phenylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
[174] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
[175] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
[176] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide,
[177] 2- (2-{[(4-chlorophenyl) sulfonyl] amino) -1,3-thiazol-4-yl) -N- (2-furylmethyl) acetamide,
[178] N-benzhydryl-2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[179] 2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N- (tetrahydro-2furanylmethyl) acetamide,
[180] Ethyl 4- {[2- (2- {[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] amino} -1- piperidinecarboxylate,
[181] N-benzhydryl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[182] 2- (2- {[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide,
[183] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[184] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diethylacetamide,
[185] 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diethylacetamide,
[186] N, N-diethyl-2- (2- {[(4-propylphenyl) sulfonyljamino} -1,3-thiazol-4-yl) acetamide,
[187] 2- (2- {[(2, 4-dichloro-6-methylphenyl) sulfonyl] amino} -1, 3-thiazol-4-yl) -N, N-diethylacetamide,
[188] N, N-diethyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[189] 2- {2-[([l, 1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diisopropylacetamide,
[190] N, N-diisopropyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiol-4-yl) acetamide,
[191] 2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diisopropylacetamide,
[192] N, N-diisopropyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[193] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diisopropylacetamide,
[194] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dipropylacetamide,
[195] N-benzyl-2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
[196] N-benzyl-2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
[197] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dimethylacetamide,
[198] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiol-4-yl) -N-cyclohexyl-N-methylacetamide,
[199] 3-chloro-N- {4- [2- (3,4-dihydro-2 (1H) -isoquinolinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2 Methylbenzenesulfonamide,
[200] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N-phenylacetamide,
[201] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-isopropyl-N methylacetamide,
[202] 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-isopropyl-N- methylacetamide,
[203] N-ethyl-N-methyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[204] 2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N-methylacetamide,
[205] N-ethyl-N-methyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[206] 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-ethyl-N-methylacetamide,
[207] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N- methylacetamide,
[208] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N [(1S) -1-phenylethyl] acet amides,
[209] 3-chloro-2-methyl-N- {4- [2-oxo-2- (1-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[210] 3-chloro-2-methyl-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[211] N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
[212] N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
[213] 2,4-dichloro-6-methyl-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl benzenesulfonamide,
[214] 2,4,6-trichloro-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[215] 3-chloro-2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[216] 2,4,6-trichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[217] 2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[218] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
[219] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
[220] 2, 4-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] 1,3-thiazol-2-yl} benzenesulfonamide,
[221] 4-chloro-2, 6-dimethyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[222] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-phenoxybenzenesulfonamide,
[223] 2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) benzenesulfonamide,
[224] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2,4-bis (trifluoromethyl) benzenesulfonamide,
[225] 4-bromo-2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[226] 4- (2-furyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[227] 3'-fluoro-6'-methoxy-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1 ' -Biphenyl] -4-sulfonamide,
[228] 4- (5-methyl-2-thienyl) -N- [4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[229] 3'-acetyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4- Sulfonamide,
[230] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4'- (trifluoromethoxy) [l, 1'- ratio Phenyl] -4-sulfonamide,
[231] 3 ', 4'-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
[232] 4- (1,3-benzodioxol-5-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzene Sulfonamide,
[233] 4- (5-chloro-2-thienyl) -N- [4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[234] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (4-pyridinyl) benzenesulfonamide,
[235] N- {4 '-{[(4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [l, 1' ratio Phenyl] -3-yl} acetamide,
[236] N- [4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (3 thienyl) benzenesulfonamide,
[237] N- [4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (2 thienyl) benzenesulfonamide,
[238] 4 '-{[(4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [1, 1'-biphenyl] -4-carboxylic acid,
[239] 4 '-(methylsulfanyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, 1'-biphenyl ] -4-sulfonamide,
[240] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3 ', 5'-bis (trifluoromethyl) [l, l'-biphenyl] -4-sulfonamide,
[241] 4'-chloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl] -4- Sulfonamide,
[242] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -l, 3-thiazol-2-yl} -3'-nitro [l, l'-biphenyl] -4- Sulfonamide,
[243] 4- (1-benzofuran-2-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[244] N- {4- [2- (morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (1-pyrrolidinyl) benzenesulfonamide,
[245] 4- (4-methyl-1-piperidinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
[246] A-anilino-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[247] 4- (benzylamino) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[248] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(2-thienylmethyl) amino] benzenesulfonamide,
[249] 4- (4-morpholinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[250] 4- (4-Methyl-l-piperazinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
[251] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(3 pyridinylmethyl) amino] benzenesulfonamide,
[252] 2,4-dichloro-6-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
[253] N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4 sulfonamide ,
[254] 2,4,6-trichloro-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[255] 3-chloro-2-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[256] 3-chloro-N- (4- {2-[(2R, 6S) -2,6-dimethylmorpholinyl] -2-oxoethyl} -1,3-thiazol-2-yl)
[257] 2-methylbenzenesulfonamide, 3-chloro-2-methyl-N- (4- {2-[(1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept-5-yl]- 2-oxoethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
[258] 3-chloro-2-methyl-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl] benzenesulfonamide,
[259] N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4- sulfonamide,
[260] N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
[261] 2,4-dichloro-6-methyl-N- [4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[262] 2,4,6-trichloro-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[263] N- {4- [2- (1,1-dioxido-4-thiomorpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
[264] Tert-butyl 4-[(2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] -piperazinecarboxylate,
[265] N- {4- [2- (4-acetyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3-chloro-2- methylbenzenesulfonamide,
[266] 3-chloro-2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluor Low Acetate,
[267] 3-chloro-2-methyl-N- {4- [2-oxo-2- (1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluoroacetate,
[268] 2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) Benzenesulfonamide,
[269] 2,4-dichloro-6-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
[270] 2,4-dichloro-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[271] 3-chloro-N- (4- {2-[(2R) -2, 4-dimethylpiperazinyl] -2-oxoethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulphone amides,
[272] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methoxy-N-methylacetamide,
[273] 3-chloro-2-methyl-N- [4- (2-oxopentyl) -1,3-thiazol-2-yl] benzenesulfonamide,
[274] 4-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
[275] 3-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[276] 3-chloro-N- [4- (3-hydroxypropyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[277] 3-chloro-N- [4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[278] 3-chloro-N- [4- (2-isopropoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[279] N- {4- [2- (benzyloxy) ethyl] -1,3-thiazol-2-yl} -3-chloro-2-methylbenzenesulfonamide,
[280] 3-chloro-N- [4- (2-methoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[281] 3-chloro-N- {4- [2- (2-fluoroethoxy) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
[282] 3-chloro-2-methyl-N- {4- [2- (2, 2,2-trifluoroethoxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[283] 3-chloro-2-methyl-N- {4- [2- (2-pyridinylsulfanyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[284] 3-chloro-2-methyl-N- {4- [2- (3-pyridinyloxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[285] Methyl 2- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethoxy] benzoate,
[286] 3-chloro-N- [5-[(dimethylamino) methyl] -4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[287] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl methanesulfonate,
[288] 3- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) propyl methanesulfonate,
[289] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl acetate,
[290] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl propionate,
[291] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-methylpropanoate,
[292] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-furoate,
[293] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl benzoate,
[294] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 4-morpholinecarboxylate,
[295] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl diethylcarbamate,
[296] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl ethylcarbamate,
[297] N- [4- (2-azidoethyl) -1, 3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
[298] N- [4- (2-aminoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
[299] 3-chloro-2-methyl-N- {4- [2- (methylamino) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[300] 4-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
[301] 3-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide hydrochloride,
[302] 3-chloro-N- {4- [2- (lH-imidazol-l-yl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide dihydrate,
[303] 3-chloro-2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) ethyl} -1,3-thiazol-2-yl} benzenesulfonamide dihydrochloride,
[304] 3-chloro-2-methyl-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
[305] 3-chloro-2-methyl-N- [4- (4-morpholinylmethyl) -1,3-thiazol-2-yl] benzenesulfonamide hydrochloride,
[306] 2,4,6-trichloro- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
[307] 2,4-dichloro-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
[308] 2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
[309] N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide hydrochloride,
[310] 3-chloro-N- {4- [2- (ethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
[311] 3-chloro-N- (4- {2-[(2-hydroxyethyl) amino] ethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulfonamide,
[312] 3-chloro-N- (4-[(2-hydroxyethyl) amino] propyl} -1,3-thiazol-2-yl) -2-methylbenzenesulfonamide hydrochloride hydrate,
[313] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N-ethylacetamide,
[314] 3-chloro-2-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[315] 3-chloro-N- {4- {2- (2-hydroxy-3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
[316] 2, 4-dichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[317] 2,4-dichloro-6-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[318] 2,4,6-trichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl) benzenesulfonamide,
[319] 4,5-dichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-thiophenesulfonamide,
[320] N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -4-phenoxybenzenesulfonamide,
[321] 3-fluoro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[322] N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -5- (2-pyridinyl) -2-thiophenesulfonamide,
[323] N- {2-chloro-4-[({4- [2-83-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} amino) sulfonyl] phenyl} acetamide ,
[324] 3-chloro-2-methyl-N- {4-[(3-oxo-4-morpholinyl) methyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[325] 3-chloro-2-methyl-N- {4- [3- (3-oxo-4-morpholinyl) propyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[326] 3-chloro-N, 2-dimethyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[327] 3-chloro-2-methyl-N- {4- [2- (2-methyl-3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[328] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] acetamide,
[329] 3-chloro-2-methyl-N- {4- [2- (3-oxo-1,4-oxazepan-4-yl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[330] 3-chloro-2-methyl-N- {4- [2- (2-oxo-1-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[331] 3-chloro-2-methyl-N- {4- [2- (2-oxo-1-imidazolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[332] 3-chloro-2-methyl-N- {4- [2- (2-oxo-1,3-oxazolidin-3-yl) ethyl] -1,3-thiazol-2-yl} benzene sulfonamide ,
[333] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N- (2-hydroxyethyl) -2 -Furamide,
[334] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N-methylcyclopropanecarboxamide,
[335] 3-chloro-2-methyl-N- {4- [2- (4-methyl-2-oxo-1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride ,
[336] 3-chloro-2-methyl-N- (4- {2-[(methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
[337] 3-chloro-2-methyl-N- (4- {2- [methyl (methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
[338] 3-chloro-2-methyl-N- [4- (2-{[trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
[339] 3-chloro-2-methyl-N- [4- (2- {methyl [(trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
[340] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -1- methyl-lH-amidazole-4- Sulfonamide,
[341] 3-chloro-N- (4- {2- [[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] ethyl} -1,3-thiazol-2-yl) -2-methylbenzene Sulfonamide,
[342] N- [4- (2-bromoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
[343] 3-chloro-N- [4- (2-chloroethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[344] 3-chloro-2-methyl-N- {4-[(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
[345] Ethyl 3- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) propanoate.
[346] Another object of the present invention is a compound as described above for use in medical applications.
[347] Another object of the invention is a process for the preparation of a compound as described above comprising at least one of the following steps:
[348] a) sulfonamide coupling by reacting 2-aminothiazole with sulfonylchloride in the presence of a base,
[349] b) sulfonamide coupling by reacting a 2-aminothiazole derivative with sulfonylchloride in the presence of a base,
[350] c) ester hydrolysis by treatment of the carboxylic acid ester with an aqueous hydroxide
[351] d) amide coupling by reacting a carboxylic ester with an amine,
[352] e) amide coupling by reacting a carboxylic acid with an amine in the presence of EDCI
[353] f) amide coupling by reacting a carboxylic acid with an amine in the presence of EDCI, HOAT or HOBT
[354] g) amide coupling by reacting a carboxylic ester with an amine in the presence of aluminum chloride,
[355] h) formation of a thiazole ring by reacting an optionally substituted thiourea with α-haloketone,
[356] i) formation of thiazole ring by reacting thiourea with ketones
[357] j) acylation of alcohols by reacting with acid chlorides in the presence of bases,
[358] k) carbamoylation of alcohols by reacting with 4-nitrophenylchloroformate and then with primary or secondary amines,
[359] 1) palladium coupling of halo compound and boronic acid,
[360] m) palladium coupling of a halo compound with an amine having 18-crown-6,
[361] n) Palladium coupling between halo compounds and amines without 18-crown-6.
[362] Another object of the invention is a method for the treatment or prevention of diabetes mellitus, syndrome X, obesity, glaucoma, hyperlipidemia, hyperglycemia, osteoporosis, tuberculosis, dementia, depression, viral diseases and inflammatory disorders, the method comprising: Administering an effective amount of their salt, hydrate or solvate to a mammal, including a person in need of such treatment.
[363] here
[364] T is an aryl ring or heteroaryl ring or aryl-Ca-alkenyl ring, optionally independently substituted by [R] n, where n is an integer from 0-5 and R is hydrogen, aryl, heteroaryl, hetero Cyclic rings, optionally halogenated C _1-6 alkyl, optionally halogenated C _1-6 alkoxy, C _1-6 -alkylsulfonyl, carboxy, cyano, nitro, halogen, optionally mono- or di-substituted amines, Optionally mono or di-substituted amide, aryloxy, arylsulfonyl, arylamino, wherein aryl, heteroaryl and aryloxy moieties and heterocyclic rings are independently of each other at one or more positions C _1-6 acyl, C ₁ -6 alkylthio, cyano, nitro, hydrogen, halogen, optionally halogenated C _1-6 -alkyl, optionally halogenated C _1-6 -alkoxy, optionally mono or di-substituted amide, (benzoylamino) methyl, Carboxy, 2-thienylmethylamino or ({[ 4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl));
[365] R ¹ is hydrogen or C _1-6 -alkyl;
[366] X is CH ₂ or CO;
[367] Y is CH ₂ , CO or a single bond;
[368] B is hydrogen, C _1-6 -alkyl or dimethylaminomethyl;
[369] R ² is C _1-6 -alkyl, azido, arylthio, heteroarylthio, halogen, hydroxymethyl, 2-hydroxyethylaminomethyl, methylsulfonyloxymethyl, 3-oxo-4-morpholinolinyl Methylene, C _1-6 -alkoxycarbonyl, 5-methyl-1,3,4-oxadiazol-2-yl;
[370] NR ₃ R ₄ , wherein R ₃ and R ₄ are each independently hydrogen, C _1-6 -alkyl, optionally halogenated C _1-6 -alkylsulfonyl, C _1-6 -alkoxy, 2-methoxyethyl, 2 Hydroxyethyl, 1-methylimidazolylsulfonyl, C _1-6 -acyl, cyclohexylmethyl, cyclopropanecarbonyl, aryl, optionally halogenated arylsulfonyl, furylcarbonyl, tetrahydro-2-furanyl Selected from methyl, N-carbetoxypiperidyl or C _1-6 -alkyl substituted with one or more aryl or heteroaryl, or
[371] NR ₃ R ₄ together is amidazole, piperidine, pyrrolidine, piperazine, morpholine, oxazepine, oxazole, thiomorpholine, 1,1 dioxidothiomorpholine, 2- (3, 4- Dihydro-2 (1H) isoquinolinyl), (1S, 4S) -2-oxa-5azabicyclo [2.2. 1] Heterocyclic system which may be hept-5-yl, which heterocyclic system is C _1-6 -alkyl, C _1-6- acyl, hydroxy, oxo, t-butoxycarbonyl May be optionally substituted;
[372] OCONR ³ R ⁴ , wherein R ³ and R ⁴ are each independently selected from hydrogen, C 1-6 alkyl, or together form morpholinyl;
[373] R ⁵ 0, wherein R ⁵ is hydrogen, optionally halogenated C _1-6 -alkyl, aryl, heteroaryl, C _1-6 -acyl, C _1-6 -alkylsulfonyl, arylcarbonyl, heteroarylcarbonyl, 2-carbomethoxyphenyl;
[374] These compounds can also be used in the manufacture of a medicament for the prevention, management or treatment of diabetes, syndrome X, obesity, glaucoma, hyperlipidemia, hyperglycemia, hyperinsulinemia, osteoporosis, tuberculosis, dementia, depression, viral diseases and inflammatory disorders.
[375] It is desirable to:
[376] T is 5-chloro-1,3-dimethyl-lH-pyrazol-4-yl; 4-chloro-2,3,1 benzoxadiazolyl; 5- (dimethylamino) -1-naphthyl; 1-methylimidazol-4-yl; 1-naphthyl;
[377] 2-naphthyl; (E) -2-phenylethenyl; 8-quinolinyl; (Benzoylamino) methyl, bromo, chloro, triisoxazolyl, 2- (methylsulfanyl) -4-pyrimidinyl, 1-methyl-5- (trifluoromethyl) pyrazol-3yl, phenylsul Thienyl substituted with one or more of polyvinyl, pyridyl;
[378] Acetylamino, 3-acetylaminophenyl, 3acetylphenyl, benzeneamino, 1,3-benzodioxol-5-yl, 2-benzofuryl, benzylamino, 3,5bis (trifluoromethyl) phenyl, bromo , Butoxy, carboxy, chloro, 4-carboxyphenyl, 3chloro-2-cyanophenoxy, 4-chlorophenyl, 5-chloro-2-thienyl, cyano, 3,4-dichlorophenyl, ({[ 4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl), fluoro, 5-fluoro-2-methoxyphenyl, 2-furyl, hydrogen , Iodo, isopropyl, methanesulfonyl, methoxy, methyl, 4-methyl-l-piperazinyl, 4-methyl-l-piperidinyl, 4methylsulfanylphenyl, 5-methyl-2-thienyl , 4-morpholinyl, nitro, 3-nitrophenyl, phenoxy, phenyl, n-propyl, 4-pyridyl, 3-pyridylmethylamino, 1-pyrrolidinyl, 2-thienyl, 3-thienyl , Substituted with one or more of 2-thienylmethylamino, trifluoromethoxy, 4-trifluoromethoxyphenyl, trifluoromethyl Phenyl; or
[379] R ¹ is hydrogen or methyl; X is CH ₂ or CO;
[380] Y is CH ₂ , CO or a single bond;
[381] B is hydrogen, methyl or dimethylaminomethyl;
[382] R ² is n-propyl, azido, bromo, chloro, 2-pyridinylsulfanyl, 3-oxo-4-morpholinolinylmethylene, ethoxycarbonyl, 5-methyl-1,3,4-oxa Diazol-2-yl, hydroxymethyl, 2-hydroxyethylaminomethyl, methylsulfonyloxymethyl;
[383] NR ³ R ⁴ , wherein R ³ and R ⁴ are each independently acetyl, benzhydryl, 1,3-benzodioxol-5-ylmethyl, benzyl, 3-chloro-2-methylphenylsulfonyl, cyclohexyl, cyclo Hexylmethyl, cyclopropanecarbonyl, ethyl, 2-furylcarbonyl, 2-furylmethyl, hydrogen, 2-hydroxyethyl, 2- (lH-indol-3-yl) ethyl, isopropyl, methoxy, 2meth Methoxyethyl, methyl, 4- (l-methylimidazolyl) sulfonyl, methylsulfonyl, phenyl, (1S) -phenylethyl, n-propyl, tetrahydro-2-furanylmethyl, trifluoromethylsulfonyl Or Ncarbetoxypiperidyl; or
[384] NR ³ R ⁴ together is 4-acetylpiperazinyl, 4-t-butoxycarbonylpiperazinyl, 2- (3, 4dihydro-2 (1H) isoquinolinyl), (2R, 6S)- 2,6-dimethylmorpholinyl, (2R) -2,4-dimethyl-1-piperazinyl, 2-hydroxy-3-oxomorpholinyl, imidazolyl, 2-methyl-3-oxomorpholinyl , 4methyl-2-oxopiperazinyl, 4-methylpiperazinyl, morpholinyl, (1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept-5-yl, 2-oxo Imidazolinyl, 3-oxomorpholinyl, 3-oxo-1, 4-oxazepinyl, 2-oxooxazolinyl, piperazinyl; Piperidinyl; Pyrrolidinyl; Pyrrolidoneyl, thiomorpholinyl; 1, 1-dioxido-thiomorpholinyl;
[385] OCONR ³ R ⁴ , wherein R ³ and R ⁴ are each independently selected from ethyl, hydrogen or together form morpholinyl;
[386] R ⁵ 0, where R ⁵ is acetyl, benzoyl, benzyl, ethyl, 2-fluoroethyl, 2-furylcarbonyl, hydrogen, isobutyryl, isopropyl, methyl, 2-carbomethoxyphenyl, methylsulfonyl, Phenyl, propionyl, 3-pyridinyl, 2,2,2-trifluoroethyl.
[387] Particular preference is given to the following compounds:
[388] Ethyl (2-{[(2, 4-dichloro-5-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[389] Ethyl 2- (2-[[(4-chlorophenyl) sulfonyl] amino] -1,3-thiazol-4-yl) acetate,
[390] Ethyl 2- (2-{[(4-chloro-2,5-dimethylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[391] Ethyl 2- (2- {[(2,4-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[392] Ethyl 2- (2-(((4-methylphenyl) sulfonyl) amino) -1,3-thiazol-4-yl) acetate,
[393] Ethyl 2- (2- {[(2, 5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[394] Ethyl (2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[395] Ethyl 2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[396] Ethyl 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
[397] Ethyl 2- (2-{[(3-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[398] Ethyl (2-{[(4-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[399] Ethyl (2-{[(4-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[400] Ethyl (2-{[(3-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[401] Ethyl (2-[(3-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[402] Ethyl (2-{[(3-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[403] Ethyl (2-{[(4-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[404] Ethyl (2-{[(3-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[405] Ethyl (2-[(phenylsulfonyl) amino] -1,3-thiazol-4-yl) acetate,
[406] Ethyl (2-{[(4-isopropylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[407] Ethyl [2-({[3-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino)- 1,3-thiazol-4-yl] acetate,
[408] Ethyl [2-({[4-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino)- 1,3-thiazol-4-yl] acetate,
[409] Ethyl (2-{[(2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[410] Ethyl [2- ({[2- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[411] Ethyl [2-({[3- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[412] Ethyl [2- ({[4- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[413] Ethyl 2- (2-{[(4-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[414] Ethyl (2-[(2-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[415] Ethyl (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[416] Ethyl (2-{[(2, 4, 6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[417] Ethyl (2- {[(2, 4-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[418] Ethyl (2-{[(5-fluoro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[419] Ethyl (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[420] Ethyl (2-{[(2-methoxy-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[421] Ethyl (2-{[(3,5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[422] Ethyl [2-({[4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[423] Ethyl (2-{[(3,4-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[424] Ethyl (2-{[(4-butoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[425] Ethyl (2-{[(4-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[426] Ethyl [2-({[4- (acetylamino) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[427] Ethyl {2-[(8-quinolinylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
[428] Ethyl (2-{[(3,4-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[429] Ethyl (2-{[(4-iodophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[430] Ethyl (2-{[(3-chloro-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[431] Ethyl [2- ({[5- (dimethylamino) -1-naphthyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[432] Ethyl (2-{[1-methyl-1H-imidazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[433] Ethyl (2-{[(5-bromo-2-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[434] Ethyl (2- {[(2, 5-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[435] ethyl. {2-[(2-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
[436] Ethyl {2-[(methylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
[437] Ethyl (2-{[(3-bromo-5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[438] Ethyl {2-[({5-[(benzoylamino) methyl] -2-thienyl} sulfonyl) amino] -1,3-thiazol-4-yl} acetate,
[439] Ethyl {2-[({5- [l-methyl-5- (trifluoromethyl) -lH-pyrazol-3-yl] -2- thienyl} sulfonyl) amino] -1,3-thiazole -4-yl} acetate,
[440] Ethyl (2-{[(4-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[441] Ethyl {2-[({5- (2-methylsulfanyl) -4-pyrimidinyl] -2-thienyl} sulfonyl) amino] -1,3thiazol-4-yl} acetate,
[442] Ethyl (2-{[(3-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[443] Ethyl (2-{[(2,4,5-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[444] Ethyl [2-({[(E) -2-phenylethenyl] sulfonyl] amino) -1,3-thiazol-4-yl] acetate,
[445] Ethyl (2-{[(2,3,4-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[446] Ethyl (2-{[(4-bromo-2, 5-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[447] Ethyl [2- ({[4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[448] Ethyl (2-{[(2, 3-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[449] Ethyl (2-{[(2-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[450] Ethyl (2-{[(4,5-dichloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[451] Ethyl [2- ({[4- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[452] Ethyl [2-({[5- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[453] Ethyl (2-{[(2,6-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[454] Ethyl (2-{[(2-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[455] Ethyl [2-({[4- (acetylamino) -3-chlorophenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[456] Ethyl (2- {[(5-chloro-1,3-dimethyl-lH-pyrazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[457] Ethyl (2-{[(3-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[458] Ethyl (2-{[(4-bromo-5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[459] Ethyl 2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
[460] Ethyl (2-{[(2, 5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[461] Ethyl [2- ({[4- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[462] Ethyl [2-{[2- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[463] Ethyl (2-{[(4-bromo-2-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[464] Ethyl (2-{[(2,3,4-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[465] Ethyl (2-{[(7-chloro-2,1,3-benzoxadiazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[466] Ethyl (2-{[(2,4,6-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[467] 2-chloro-5-({4- (2-methoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} sulfonyl) -4-fluorobenzoic acid,
[468] Ethyl (2-{[(5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[469] Ethyl (2-{[(2-chloro-4-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[470] Ethyl [2-({[5- (3-isoxazolyl) -2-thienyl] sulfonyl} amino) -1, 3-thiazol-4-yl] acetate,
[471] Ethyl (2-{[(4-bromo-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[472] Ethyl (2-{[(4-phenoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[473] Ethyl (2-{[4-chloro-2, 6-dimethylphenyl) sulfonyl amino} -1,3-thiazol-4-yl) acetate,
[474] Ethyl [2-({[2-methyl-4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[475] Ethyl [2-(([2,4-bis (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
[476] Ethyl 2- {2-[[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] -1,3-thiazol-4-yl} acetate,
[477] Ethyl oxo (2-[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[478] Ethyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) (oxo) acetate,
[479] Ethyl oxo (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[480] Ethyl {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} (oxo) acetate,
[481] Ethyl (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) (oxo) acetate,
[482] 2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
[483] 2- (2-{[(2,5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
[484] (2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
[485] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
[486] Isopropyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[487] Phenyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[488] Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[489] Methyl 2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -5-methyl-1,3-thiazol-4-yl} acetate,
[490] Methyl (2-{[(4-chlorophenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
[491] Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
[492] Methyl [2-({[4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -5-methyl-1,3-thiazol-4-yl] acetate,
[493] Methyl (5-methyl-2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[494] Methyl (5-methyl-2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
[495] Methyl (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
[496] N- (2-methoxyethyl) -2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[497] 2- (2-{[(2, 5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
[498] N- (1,3-benzodioxol-5-ylmethyl) -2- {2- [(l-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
[499] N- (2-furylmethyl) -2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
[500] 2- (2-{[(2,4-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
[501] N-isopropyl-2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
[502] N- [2- (1H-indol-3-yl) ethyl] -2- {2- [1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
[503] N- (cyclohexylmethyl) -2- {2-[(phenylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
[504] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
[505] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
[506] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide,
[507] 2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N- (2furylmethyl) acetamide,
[508] N-benzhydryl-2- (2- {[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[509] 2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N- (tetrahydro-2furanylmethyl) acetamide,
[510] Ethyl 4-{[2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] amino} -1 piperidinecarboxylate,
[511] N-benzhydryl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[512] 2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide,
[513] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[514] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diethylacetamide,
[515] 2- {2- [([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diethylacetamide,
[516] N, N-diethyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[517] 2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diethylacetamide,
[518] N, N-diethyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[519] 2- {2-[([1-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diisopropylacetamide,
[520] N, N-diisopropyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[521] 2- (2- {[(2, 4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N- diisopropylacetamide,
[522] N, N-diisopropyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl amino} -1,3-thiazol-4-yl) acetamide,
[523] 2- (2-[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diisopropylacetamide,
[524] 2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dipropylacetamide,
[525] N-benzyl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
[526] N-benzyl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N ethylacetamide,
[527] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dimethylacetamide,
[528] 2- (2-[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-cyclohexyl-N-methylacetamide,
[529] 3-chloro-N- {4- [2- (3,4-dihydro-2 (1H) -isoquinolinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2 Methylbenzenesulfonamide,
[530] 2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N-phenylacetamide,
[531] 2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-isopropyl-N- methylacetamide,
[532] 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-isopropyl-N- methylacetamide,
[533] N-ethyl-N-methyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[534] 2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N- methylacetamide,
[535] N-ethyl-N-methyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
[536] 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-ethyl-N methylacetamide,
[537] 2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N- methylacetamide,
[538] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N-[(1S) -1-phenylethyl] Acetamide,
[539] 3-chloro-2-methyl-N- {4- [2-oxo-2- (l-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[540] 3-chloro-2-methyl-N- {4- [2-oxo-2- (l-piperidinyl) ethyl] -1, 3-thiazol-2-yl} benzenesulfonamide,
[541] N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
[542] N- {4- [2-oxo-2- (l-piperidinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
[543] 2,4-dichloro-6-methyl-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[544] 2,4,6-trichloro-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[545] 3-chloro-2-methyl-N-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[546] 2,4, 6-trichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[547] 2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[548] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl] -4-sulfonamide,
[549] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
[550] 2, 4-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[551] 4-chloro-2, 6-dimethyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[552] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4 phenoxybenzenesulfonamide,
[553] 2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) benzenesulfonamide,
[554] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2,4-bis (trifluoromethyl) benzenesulfonamide,
[555] 4-bromo-2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[556] 4- (2-furyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[557] , 3'-fluoro-6'-methoxy-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1 '-Biphenyl] -4-sulfonamide,
[558] 4- (5-methyl-2-thienyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[559] 3'-acetyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4- Sulfonamide,
[560] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4 '-(trifluoromethoxy) [1,1'-ratio Phenyl] -4-sulfonamide,
[561] 3 ', 4'-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] 4-sulfonamide,
[562] 4- (1,3-benzodioxol-5-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazole-2y1} benzenesulfonamide ,
[563] 4- (5-chloro-2-thienyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[564] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (4-pyridinyl) benzenesulfonamide,
[565] N- {4 '-[({4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [l, l'- Biphenyl] -3-yl} acetamide,
[566] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (3-thienyl) benzenesulfonamide,
[567] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (2-thienyl) benzenesulfonamide,
[568] 4 '-[({4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [l, l'-biphenyl] -4-carboxylic acid,
[569] 4 '-(methylsulfanyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl ] -4-sulfonamide,
[570] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3 ', 5'-bis (trifluoromethyl) [1, l'-biphenyl] -4-sulfonamide,
[571] 4'-Chloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4- Sulfonamide,
[572] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3'-nitro [1,1'-biphenyl] -4 sulfone amides,
[573] 4- (1-benzofuran-2-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[574] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (1-pyrrolidinyl) benzenesulfonamide,
[575] 4- (4-methyl-1-piperidinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
[576] 4-anilino-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[577] 4- (benzylamino) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[578] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(2-thienylmethyl) amino] benzenesulfonamide,
[579] 4- (4-morpholinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[580] 4- (4-methyl-1-piperazinyl) -N-{-[2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[581] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(3 pyridinylmethyl) amino] benzenesulfonamide,
[582] 2,4-dichloro-6-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
[583] N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4 sulfonamide ,
[584] 2,4,6-trichloro-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[585] 3-chloro-2-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[586] 3-chloro-N- (4- {2- [(2R, 6S) -2,6-dimethylmorpholinyl] -2-oxoethyl} -1,3-thiazol-2-yl) 2-methylbenzene Sulfonamide,
[587] 3-Chloro-2-methyl-N- (4- {2-[(1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept-5-yl] -2-oxoethyl} -l , 3-thiazol-2-yl) benzenesulfonamide,
[588] 3-chloro-2-methyl-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[589] N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
[590] N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
[591] 2,4-dichloro-6-methyl-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[592] 2,4,6-trichloro-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1, 3-thiazol-2-yl} benzenesulfonamide,
[593] N- {4- [2- (1,1-dioxido-4-thiomorpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
[594] Tert-butyl 4- [(2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] 1-piperazinecarboxylate,
[595] N- {4- [2- (4-acetyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3-chloro-2-methylbenzenesulfonamide,
[596] 3-chloro-2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluor Low Acetate,
[597] 3-chloro-2-methyl-N- {4- [2-oxo-2- (1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluoroacetate,
[598] 2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) Benzenesulfonamide,
[599] 2, 4-dichloro-6-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
[600] 2,4-dichloro-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[601] 3-chloro-N- (4- {2-[(2R) -2,4-dimethylpiperazinyl] -2-oxoethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulphone amides,
[602] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methoxy-N- methylacetamide,
[603] 3-chloro-2-methyl-N- [4- (2-oxopentyl) -1,3-thiazol-2-yl] benzenesulfonamide,
[604] 4-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
[605] 3-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[606] 3-chloro-N- [4- (3-hydroxypropyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[607] 3-chloro-N- [4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[608] 3-chloro-N- [4- (2-isopropoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[609] N- {4- [2- (benzyloxy) ethyl] -1,3-thiazol-2-yl} -3-chloro-2-methylbenzenesulfonamide,
[610] 3-chloro-N- [4- (2-methoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[611] 3-chloro-N- {4- [2- (2-fluoroethoxy) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
[612] 3-chloro-2-methyl-N- {4- [2- (2, 2,2-trifluoroethoxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[613] 3-chloro-2-methyl-N- {4- [2- (2-pyridinylsulfanyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[614] 3-chloro-2-methyl-N- {4- [2- (3-pyridinyloxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[615] Methyl 2- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethoxy] benzoate,
[616] 3-chloro-N- [5-[(dimethylamino) methyl] -4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[617] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl methanesulfonate,
[618] 3- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) propyl methanesulfonate,
[619] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl acetate,
[620] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl propionate,
[621] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-methylpropanoate,
[622] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-furoate,
[623] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl benzoate,
[624] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 4-morpholinecarboxylate,
[625] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) ethyl diethylcarbamate,
[626] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl ethylcarbamate,
[627] N- [4- (2-azidoethyl) -1, 3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
[628] N- [4- (2-aminoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
[629] 3-chloro-2-methyl-N- {4- [2- (methylamino) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[630] 4-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
[631] 3-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide hydrochloride,
[632] 3-chloro-N- {4- [2- (lH-imidazol-1-yl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide dihydrate,
[633] 3-chloro-2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide dihydrochloride,
[634] 3-chloro-2-methyl-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
[635] 3-chloro-2-methyl-N- [4- (4-morpholinylmethyl) -1,3-thiazol-2-yl] benzenesulfonamide hydrochloride,
[636] 2,4,6-trichloro-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
[637] 2,4-dichloro-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
[638] 2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
[639] N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide hydrochloride,
[640] 3-chloro-N- {4- [2- (ethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
[641] 3-chloro-N- (4- {2-[(2-hydroxyethyl) amino] ethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulfonamide,
[642] 3-chloro-N- (4- {3-[(2-hydroxyethyl) amino] propyl} -1,3-thiazol-2-yl) -2 methylbenzenesulfonamide hydrochloride hydrate,
[643] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N ethylacetamide,
[644] 3-chloro-2-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2 -yl} benzene sulfonamide,
[645] 3-chloro-N- {4- [2- (2-hydroxy-3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
[646] 2,4-dichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[647] 2,4-dichloro-6-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[648] 2,4,6-trichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[649] 4,5-dichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-thiophenesulfonamide,
[650] N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -4 phenoxybenzenesulfonamide,
[651] 3-fluoro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[652] N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -5- (2-pyridinyl) -2- thiophensulfonamide,
[653] N- {2-chloro-4-[({4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} amino) sulfonyl] phenyl} acet amides,
[654] 3-chloro-2-methyl-N- {4-[(3-oxo-4-morpholinyl) methyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[655] 3-chloro-2-methyl-N- {4- [3- (3-oxo-4-morpholinyl) propyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[656] 3-chloro-N, 2-dimethyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[657] 3-chloro-2-methyl-N- {4- [2- (2-methyl-3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[658] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] acetamide,
[659] 3-chloro-2-methyl-N- {4- [2- (3-oxo-1,4-oxazepan-4-yl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[660] 3-chloro-2-methyl-N- {4- [2- (2-oxo-1-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[661] 3-chloro-2-methyl-N- {4- [2- (2-oxo-1-imidazolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[662] 3-chloro-2-methyl-N- {4- [2- (2-oxo-1,3-oxazolidin-3-yl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
[663] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N- (2-hydroxyethyl) -2 -Furamide,
[664] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) ethyl] -N methylcyclopropanecarboxamide,
[665] 3-chloro-2-methyl-N- {4- [2- (4-methyl-2-oxo-1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride ,
[666] 3-chloro-2-methyl-N- (4- {2-[(methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
[667] 3-chloro-2-methyl-N- (4- {2- [methyl (methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
[668] 3-chloro-2-methyl-N- [4- (2-{[(trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
[669] 3-chloro-2-methyl-N- [4- (2- {methyl [(trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
[670] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -1methyl-lH-amidazole-4-sulphone amides,
[671] 3-chloro-N- (4- {2-[[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] ethyl} -1,3 thiazol-2-yl) -2-methylbenzenesulphone amides,
[672] N- [4- (2-bromoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
[673] 3-chloro-N- [4- (2-chloroethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
[674] 3-chloro-2-methyl-N- {4-[(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
[675] Ethyl 3- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) propanoate.
[676] Another object of the present invention is a pharmaceutical composition comprising at least one compound of formula (II) as defined above, and a pharmaceutically acceptable carrier.
[677] The compounds according to the invention can be used in several indications involving 11-β-hydroxysteroid dehydrogenase type 1 enzyme. Thus, the compounds according to the invention can be used for dementia (see WO97 / 07789), osteoporosis (Canalis E 1996, Mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis, Journal of Clinical Endocrinology and Metabolism, 81,3441-344). Inhibition of Thl immune response by glucocorticoid: dexamethasone selectively inhibits IL-12-induced Stat 4 phosphorylation in T lymphocytes ", The journal of Immunology 2000, Feb 15, vol 164 (4), pages 1768-74) and the indications listed above.
[678] Various terms used individually and in combination in the above definitions of compounds having Formula II will be described.
[679] As used herein, the term "aryl" is intended to include aromatic rings (monocyclic or cyclic) having about 6 to 10 ring carbon atoms, such as phenyl (Ph) and naphthyl, optionally C _1-6- It may be substituted by alkyl. Examples of substituted aryl groups are benzyl, and 2-methylphenyl.
[680] As used herein, the term "heteroaryl" refers to a bi- or tricyclic aromatic having 5 to 14, preferably 5 to 10 ring atoms, such as 5,6,7,8,9 or 10 ring atoms (mono- or cyclic) It refers to a ring system (only one ring is needed for aromatics), wherein one or more ring atoms are carbon-free, such as nitrogen, sulfur, oxygen and selenium. Examples of such heteroaryl rings are pyrrole, amidazole, thiophene, furan, thiazole, isothiazole, thiadiazole, oxazole, isoxazole, oxadiazole, pyridine, pyrazine, pyrimidine, pyridazine, pyrazole , Triazole, tetrazole, chromman, isochroman, quinoline, quinoxaline, isoquinoline, phthalazine, cynoline, quinazoline, indole, isoindole, indolin, isoindolin, benzothiophene, benzofuran , Isobenzofuran, benzoxazole, 2,1,3-benzoxadiazole, benzothiazole, 2,1,3-benzothiazole, 2,1,3-benzoselenadiazole, benzamidazole, Sol, benzodioxane, indane, 1,2,3,4-tetrahydroquinoline, 3,4-dihydro-2H-1,4-benzoxazine, 1,5-naphthyridine, 1,8-naphthyridine , Acridine, phenazine and xanthene.
[681] As used herein, the term “heterocyclic” is partially and with 4 to 14, preferably 4 to 10 ring atoms, such as, for example, a corresponding partially saturated or heterocyclic ring as well as a heteroaryl group. It is intended to include fully saturated single, di- and tricyclic rings as well as unsaturated ones. Examples of saturated heterocyclic rings are azetidine, pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine and 1,4-oxazepan.
[682] In the compounds of the formula (II) according to the present application, which may be linear, branched or cyclic, C _1-6 -alkyl is preferably C _1-4 -alkyl. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, isohexyl, and cyclohexyl.
[683] In the compounds of the formula (II) according to the present application which may be linear or branched, C _1-6 -alkoxy is preferably C _1-4 -alkoxy. Examples of alkoxy groups include methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, hexyloxy, and isohexyloxy.
[684] In the compounds of formula (II) according to the present application, C _1-6 -acyl may be saturated or unsaturated and is preferably C _1-4 -acyl. Examples of acyl groups include formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, butenoyl (eg 3-butenoyl), hexenoyl (eg 5-hexeno It includes)
[685] As used herein, the term "halogen" is intended to include fluorine, chlorine, bromine and iodine.
[686] As used herein, the term "sulfanyl" refers to a thio group.
[687] As mono- or di-substituted herein, the functional groups in question are H, C _1-6 -acyl, C _1-6 -alkenyl, C _1-6- (cyclo) alkyl, aryl, pyridylmethyl, Or heterocyclic rings eg azetidine, pyrrolidine, piperidine, piperazine, morpholine and thiomorpholine, and the heterocyclic ring is optionally substituted with C _1-6 -alkyl It can be.
[688] As used herein, the term "prodrug form" means a pharmaceutically acceptable derivative, such as an ester or an amide, which derivative is biotransformed in the body forming the active drug (Goodman and Gilman's, The Pharmacological basis of Therapeutics, 8th). ed., McGraw-Hill, hit.Ed. 1992, "Biotransformation of Drugs, p. 13-15).
[689] As used herein, "pharmaceutically acceptable" means that it is generally useful for preparing safe, non-toxic, biologically desirable and otherwise desirable pharmaceutical compositions, including those useful for veterinary as well as human pharmaceutical use. do.
[690] "Pharmaceutically acceptable salt" means a salt that is pharmaceutically acceptable and has the desired pharmacological activity, as defined above herein. Such salts include hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, acetic acid, glycolic acid, maleic acid, malonic acid, oxalic acid, methanesulfonic acid, trifluoroacetic acid, fumaric acid, succinic acid, tartaric acid, citric acid, benzoic acid, ascorbic acid, and the like. Acid addition salts formed with organic and inorganic acids. Base addition salts may be formed with organic and inorganic bases, such as sodium, ammonia, potassium, calcium, ethanolamine, diethanolamine, N-methylglucamine, choline and the like.
[691] The pharmaceutical composition according to the invention contains a pharmaceutically acceptable carrier with at least one compound comprising formula (II) as defined above, dissolved or dispersed therein as an active, antimicrobial component. In a preferred embodiment, the therapeutic composition is not immunogenic when administered to a human patient for the purpose of treatment unless the purpose is to elicit an immune response.
[692] Formulations of pharmacological compositions containing the active ingredients dissolved or dispersed therein are well understood in the art. Typically such compositions are prepared as sterile injectables in liquid solution or suspension, aqueous or non-aqueous, but may also be prepared in liquid form, or suspension, suitable for use as a liquid before use. The formulations may also be emulsified.
[693] The active ingredient may be mixed with an excipient in an amount that is pharmaceutically acceptable and compatible with the active ingredient and suitable for use in the therapies described herein. Suitable excipients are, for example, water, saline, dextrose, glycerol, ethanol or others of that kind and combinations thereof. In addition, if desired, the composition may contain small amounts of auxiliary substances such as wetting or emulsifying agents, pH buffers, and the like, which enhance the effectiveness of the active ingredient.
[694] Pharmaceutically acceptable carriers are well known in the art. Examples of liquid carriers are sterile aqueous solutions containing no substances in addition to the active ingredient and water, or containing buffers such as sodium phosphate, physiological saline, or both, at physiological pH values. Still more, the aqueous carrier may contain one or more buffering salts, as well as salts such as sodium chloride and potassium chloride, dextrose, propylene glycol, polyethylene glycol and other solutes.
[695] The liquid composition may also contain a liquid phase in addition to and excluding water. Examples of such additive liquid phases are glycerin, vegetable oils such as cottonseed oil, organic esters such as ethyl oleate, and water-oil emulsions.
[696] A pharmaceutical composition according to one of the preferred embodiments of the present invention, including a compound comprising Formula II, may comprise a pharmaceutically acceptable salt of that component therein as described above. Pharmaceutically acceptable salts include, for example, acid addition salts (formed from free amino groups of the polypeptide) formed with inorganic acids such as hydrochloric acid or phosphoric acid, or organic acids such as acetic acid, tartaric acid and mandelic acid. Salts formed with free carboxyl groups are also derived from, for example, inorganic bases such as sodium, potassium, ammonium, calcium hydroxide or ferric hydroxide and organic bases such as isopropylamine, trimethylamine, 2-ethylamino ethanol, histidine, procaine and the like. Can be induced.
[697] Formulations according to a preferred embodiment may be administered orally, locally, intraperitoneally, intraarticularly, intracranially, intracutaneously, intramuscularly, intraocularly, intra meningically, intravenously, subcutaneously. Other routes known to those skilled in the art are also conceivable.
[698] Orally administrable compositions according to the invention may be in the form of tablets, capsules, powders, granules, lozenges, liquid or gel preparations, such as oral, topical or sterile parenteral solutions or suspensions. Tablets and capsules for oral administration may be in the form of unit dosage forms and include, for example, conventional excipients such as syrup, acacia, gelatin, sorbitol, traganas or polyvinyl-pyrrolidone; Fillers such as, for example, lactose, sugar, corn-starch, calcium phosphate, sorbitol or glycine; Tableting lubricants such as magnesium stearate, talc, polyethylene glycol or silica; For example, it may contain a disintegrant such as potato starch, or an acceptable wetting agent such as sodium lauryl sulfate. Tablets may be coated according to methods well known in the normal pharmaceutical practice. Oral liquid formulations can be, for example, in the form of aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or as dry products for reconstitution with water or other suitable solution prior to use. Such liquid preparations include, for example, suspending agents such as sorbitol, syrup, methyl cellulose, glucose syrup, gelatin hydrogenated edible fats; Non-aqueous solutions (which may include edible oils) such as emulsifiers such as lecithin, sorbitan monooleate or acacia, for example almond oil, fractionated coconut oil, glycerin, propylene glycol, or oily esters such as ethyl alcohol ; For example, it may contain conventional additives such as preservatives such as methyl or propyl p-hydroxybenzoate or sorbic acid and, if desired, conventional flavoring or coloring agents.
[699] The pharmaceutical composition according to the invention may comprise an amount of typically at least 0.1% by weight of the compound comprising formula II per weight of the total therapeutic composition. % By weight is the weight ratio of the total composition. Thus, for example, 0.1% by weight is 0.1 gram of the compound comprising Formula II per 100 grams of the total composition. Appropriate daily oral dosages for stray oil, preferably humans, can vary greatly depending on the condition of the patient. However, a dosage of a compound comprising Formula II of about 0.1 to 300 mg / kg body mass may be appropriate.
[700] The compositions according to the invention can also be used veterinarily and therefore they can comprise a veterinary acceptable excipient or carrier.
[701] The compounds of the present invention can be used as diagnostic agents in labeled form, eg, in isotopically labeled form.
[702] The compounds of formula (II) can be prepared by or in analogy to conventional methods, in particular according to or analogous to the following methods. Moreover, in vitro pharmaceuticals were studied using the following reagents and methods.
[703] All publications mentioned herein are incorporated herein by reference. The expression "consisting of" is understood to include but is not limited to this. Thus, other non-mentioned substances, additives or carriers may be present.
[704] The invention will be explained with reference to the following figures and examples. These drawings and embodiments are not to be considered as limiting the scope of the invention, but should serve only in the manner of illustration.
[705] Flash Proximity Method
[706] [1,2 (n) ^-3 H] -cortisone was purchased from Amersham Pharmacia Biotech. Anti-cortisol monoclonal mouse antibody, clone 6D6.7, was obtained from Immunotech and coated with monoclonal antimouse antibody and Scintillation Proximity Assay (SPA) beads were obtained from Amersham Pharmacia Biotech. NADPH, tetrasodium salt was from Calbiochem and glucose-6-phosphate (G-6-P) was supplied from Sigma. Human 11-β-hydroxysteroid dehydrogenase type 1 enzyme (11-β-HSD ₁ ) was expressed as Pichia pastoris . 18-β-glyciletinic acid (GA) was obtained from Sigma. Subsequent dilution of the compound was carried out in Tecan Genesis RSP 150. The compound was dissolved in DMSO (1 mM) and diluted in 50 mM Tris-HC1, pH 7.2 containing 1 mM EDTA.
[707] Plate propagation was performed on WallacQuadra. The amount of product [ ³ H] -cortisol bound to the beads was determined on a Packard, Top Count microplate liquid scintillation counter.
[708] 11-β-HSC ₁ enzyme assay with 1 mM EDTA, substrate mixture tritium cortisone / NADPH (175 nM / 181 μM), G-6-P (1 mM) and serially diluted inhibitors (9 to 0.15 μM) This was performed in a 96 well microtiter plate (Packard, Optiplate) with a total well volume of 220 μL containing 30 mM Tris-HCl, pH 7.2. The reaction was initiated by the addition of human 11-β-HSD ₁ , either as a Pichia pastoris cell homogenate or a microsome prepared from Pichia pastoris (the final amount of enzyme used varied between 0.057 and 0.11 mg / mL). Following mixing, the plate was shaken for 30-45 minutes at room temperature. The reaction was terminated with 10 μL 1 mM GA stop solution. Monoclonal mouse antibody was then added (10 μL of 4 μM) followed by 100 μL (suspended according to manufacturer's instructions) of SPA beads. Appropriate control started by omitting 11-β-HSD ₁ to obtain nonspecific binding (NSB) values.
[709] The plates were incubated in a shaker for 30 minutes at room temperature before covering and counting with plastic film. The amount of [ ³ H] -cortisol bound to the beads was determined on a microplate liquid scintillation counter.
[710] Calculation of Ki values for inhibitors was performed by using Activity Base. Ki values are calculated from IC ₅₀ and Km values are calculated using the Cheng Prushoff equation (reversible inhibition following the Michaelis-Menten equation): Ki = IC50 (1+ [S] / Km) [Cheng, YC; Prushoff, WH Biochem. Pharmacol. 1973, 22, 3099-3108. IC ₅₀ is measured experimentally in the assay where the reduction of cortisone turnover is dependent on the inhibitory potential of the respective substance. Ki values of the compounds of the present invention for 11-β-HSD ₁ are typically between about 10 nM and about 10 μM. The following Ki values, which are illustrative of the present invention, were determined by human 11-β-HSD ₁ enzyme assay (see Table 1).
[711] Ki value determined by human 11-β-HSD ₁ enzyme analysis Example Compound Ki (nM) 1A32 149A51 151A21 179A14 181A53 189A299 204A91
[712] Compound manufacture
[713] Normal:
[714] For preparative straight phase HPLC purification, use a Phenomenex column (250 x 21.1 mm, 10 μm) on a Gilson system eluting with ethanol in chloroform (gradient from 0-10% for 10 minutes) with a flow of 20 mL / min. It was. Column chromatography is performed on silica using silica gel 60 (230-400 mesh); Merck. Melting points were determined on a Gallenkamp instrument. Elemental analysis was recorded using the Vario EL device. HPLC analysis was performed using a Hypersil Elite column (150 × 4.6 mm, 3μ) with a flow of 3 mL / min in a Waters 600E system while monitoring at 254 nm. Reverse phase preparative HPLC is a 100 × 21.2 mm, 5μ Hypersil Elite column eluting with a gradient of 95% ACN in 5% water to 5% ACN (0.2% TFA buffer) in 95% water over 10 minutes at a flow rate of 20 mL / min. Performed with a UV detector set at 254 nm. Thin layer chromatography was performed using a previously coated silica gel F-254 plate (0.25 mm thick). Electrospray MS Stack was obtained on a Micromass platform LCMS spectrometer. The crude, reaction finished compound was subjected to flash column chromatography using a silica SPE column (10 g silica) prepacked on an Isco Foxy 200 Combiflash system, with a gradient of 16.67% ethyl acetate in hexane incrementally increased to 100% ethyl acetate. Purification by
[715] List of abbreviations
[716] DCM = dichloromethane
[717] DIEA = N, N-diisopropylethylamine
[718] DMAP = 4-dimethylaminopyridine
[719] DME = ethylene glycol dimethyl ether
[720] DMF = Dimethylformamide
[721] DMSO = dimethyl sulfoxide
[722] EDCI = 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride
[723] EDTA = ethylenediaminetetraacetic acid
[724] HCOOH = formic acid HOAT = l-hydroxy-7-azabenzotriazole
[725] HOBT = 1-hydroxybenzotriazole hydrate
[726] MTBE = tert-butyl methyl ether
[727] TEA = triethylamine
[728] THF = tetrahydrofuran
[729] Sulfonamide Coupling:
[730] Method A:
[731] 1 Eq of 2-aminothiazole was dissolved in pyridine (0.5 M solution). Sulfonyl chloride (1.2 eq) was added and the reaction mixture was stirred at ambient temperature for 15 hours under nitrogen atmosphere. The reaction mixture was poured into aqueous HCl (1M). If the product precipitated, it was collected in a filter, washed with aqueous HCl (1M) and recrystallized with ethanol. If an oil was obtained, the raw material was extracted with DCM, reaction finished and purified using standard procedures.
[732] Method B:
[733] A solution of 2-aminothiazole derivative (1 eq), triethylamine (2 eq) and DMAP (1 eq) in DMF (1 M) and DCM (0.225 M) was partitioned into reaction vials. Sulfonyl chloride (1.2 eq) was dissolved in DCM (0.33 M) and added. The reaction mixture was kept at room temperature overnight. The mixture was then added to petroleum ether (10-fold reaction volume). After several hours in the freezer the supernatant was decanted and the remaining material (part of) dissolved in DMSO-methanol-acetic acid (300 μL + 500 μL + 50 μL) and purified by preparative LCMS (acetonitrile-water component). The purest portion was collected and lyophilized. As an alternative, the raw materials were separated using extraction finishing and purified using standard procedures.
[734] Ester hydrolysis:
[735] Method C:
[736] An ester of 1 Eq was suspended in 95% ethanol (0.1 M) and treated with KOH (aq. 6 eq). Water was added until a clear solution was obtained. The reaction mixture was stirred at ambient temperature for 2-3 hours. The solvent was removed under reduced pressure and the raw material was redissolved in water. Concentrated HCl was added until pH 2 to give a precipitate which was collected in a filter, washed with cold water and dried.
[737] Amide coupling:
[738] Method D:
[739] The carboxylic ester was dissolved (0.05 M) in large excess of amine in 40 or 70% aqueous-solution. The reaction mixture was stirred at ambient temperature overnight. The solvent was removed under reduced pressure and the crude product was purified by flash column chromatography on silica gel eluting with methanol (0-> 6%) in DCM.
[740] Method E:
[741] The carboxylic acid was suspended in DCM (0.05M) followed by the addition of EDCI (1.1 eq), triethylamine (3 eq), DMAP (0.5 eq) and selected amines (1.2 eq). DMF was added when the starting material did not dissolve properly. The reaction mixture was stirred at ambient temperature overnight. The organic phase was washed with aqueous HCl (1M) and dried over sodium sulphate, filtered and evaporated in vacuo. The crude product amide was purified by flash column chromatography on silica gel, eluting with methanol (1-> 3-> 6%) or ethyl acetate in DCM.
[742] Method F:
[743] The carboxylic acid was suspended in DCM (0.1 M) and cooled to 0 ° C. under nitrogen (g) atmosphere. EDCI (1 eq), HOAT (1 eq) or HOBT (1 eq) was added followed by TEA (2.2 eq). After 10 minutes, the optional amine (1.2 eq) was added and the reaction mixture was warmed to ambient temperature. After 5 hours, the DCM phase was washed with aqueous HCl (1M), reaction finished and purified as described in Method E.
[744] Method G:
[745] Under N ₂ -atmosphere, aluminum chloride (1 eq) was suspended in DCM (0.1 M) and treated with amine (4eq) of choice at ambient temperature. After 10 minutes, alkyl ester (1 eq) was added and the reaction mixture was stirred (TLC) until the starting material was consumed. Quench with saturated aqueous sodium hydrogen carbonate or aqueous HC1 (1 M) and finish extraction with ethyl acetate to afford the crude product which was then purified by flash chromatography on silica gel eluting with a DCM / methanol mixture.
[746] Formation of Thiazole Rings:
[747] Method H:
[748] To a solution or suspension of (substituted) thiourea in ethanol (0.5 M) was added 1 equivalent of α-haloketone at room temperature. The reaction mixture was stirred for 4 h at 95 ° C. in a sealed tube, cooled, concentrated, redissolved in ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, dried over sodium sulphate, petroleum as eluent Chromatography on silica gel using ether and ethyl acetate.
[749] Method I:
[750] To a 0.5 M solution of ketone (1 eq) and thiourea (2 eq) in ethanol at 60 ° C., 1 eq of iodine was added at a time. The reaction tube was sealed and the reaction mixture was stirred at 100 ° C. for 16 h. After evaporation of the solvent the residue was taken up in DCM, washed with saturated aqueous sodium hydrogen carbonate and dried over magnesium sulfate. The product was purified by chromatography on silica gel using a gradient of 8: 1 to 2: 1 petroleum-ether / ethyl acetate for elution.
[751] Acylation:
[752] Method J:
[753] To a solution of alcohol in dry pyridine (0.3 M), 1.1 eq of acid chloride was added at 0 ° C. The reaction mixture is stirred at rt for 6 h, concentrated, co-evaporated with acetonitrile, redissolved in DCM, washed with aqueous HCl (0.5M), dried over sodium sulfate, petroleum as eluent Chromatography on silica gel using ether and ethyl acetate.
[754] Carbamate:
[755] Method K:
[756] To an alcohol solution (0.3 M) in dry pyridine was added 1.5 eq of 4-nitrophenyl chloroformate (0.5 M in dry pyridine) at 0 ° C. The reaction mixture was stirred at rt for 12 h before 5 eq of primary or secondary amine was added at 0 ° C. The solution is stirred at room temperature for 3 hours, concentrated, co-evaporated with acetonitrile, redissolved in DCM, washed with aqueous HCl (0.5M) and saturated aqueous sodium bicarbonate, dried over sodium sulfate and dissolved Chromatography on silica gel using DCM and methanol as the reagent.
[757] Palladium Coupling:
[758] Method L:
[759] Intermediate 18 (50 mg, 0.10 mmol) and boronic acid (0.15 mmol) were weighed into the reaction tube with palladium (II) acetate (2 mg). Dioxane (1.0 mL) was added followed by aqueous potassium carbonate (100 μL, 2 M). The mixture was stirred at 80 ° C. and the starting material was consumed (2-20 hours). The solvent was evaporated and the material dissolved in acetic acid-acetonitrile (400 μL-600 μL) and purified by preparative HPLC using an acetonitrile-water gradient containing 0.1% acetic acid. After HPLC analysis, the purest portion was collected and lyophilized.
[760] Method M:
[761] Intermediate 18 (50 mg, 0.10 mmol), 18-crown-6 (37 mg, 0.14 mmol), (R)-(+)-2,2'-bis (diphenylphosphino) 1, l'-ratio Naphthyl (3.7 mg, 6 pool), tris (dibenzylidene-acetone) dipalladium (0) (1.8 mg, 2 tmol), sodium tert. Butoxide (13.5 mg, 0.14 mmol) and amine (0.15 mmol) were weighed into the reaction mixture tube under nitrogen atmosphere. Dry dioxane (800 μL) was added and the mixture was stirred at 80 ° C. until the starting material was consumed (2-3 hours). The solvent was evaporated and the material was purified by preparative LCMS using an acetonitrile-water gradient containing 0.1 acetic acid. After HPLC analysis, the purest portion was collected and lyophilized.
[762] Method N:
[763] Intermediate 18 (50 mg, 0.10 mmol), (R)-(+)-2,2'-bis (diphenylphosphino) l, 1'- vinaphthyl (3.7 mg, 6 μmol), tris (dibenzylidene Acetone) dipalladium (0) (1.8 mg, 2 μmol) and sodium tert.butoxide (29 mg, 0.30 mmol) were weighed into the reaction tube under nitrogen atmosphere. Amine (1.0 mmol) was dissolved in dry toluene (300 μL) and added. The reaction mixture was stirred overnight at 80 ° C. The material was purified by preparative LCMS using acetonitrile-water gradient containing 0.1% acetic acid. After HPLC analysis, the purest portion was collected and lyophilized.
[764] Sulfonyl chloride
[765] Arylsulfonyl chloride (for Example 40, 77M-77Q, 154A-158A), which is not commercially available, was prepared from aniline derivatives according to literature procedures (see, eg, Hoffman, RV (1981) Org. Synth. 60 : 121).
[766] Intermediate
[767] Intermediate 1
[768] Ethyl {2-[(tert-butoxycarbonyl) amino] -1,3-thiazol-4-yl} acetate
[769] Ethyl 2-amino-4-thiazolyl acetate (25.0 g, 134 mmol) was suspended in 75 g tert-butanol. DMAP (1.6 g, 10 mol%) was added at 40 ° C. Boc-anhydride (32.0 g, 147 mmol) was added over 30 minutes. The suspension was stirred for 2.5 hours (after 2 hours gas evolution stopped), the mixture was diluted with a large amount of water and extracted with a toluene-heptane (30/60) mixture. The organic phase was washed with sodium hydrogen sulfate solution, dried over magnesium sulfate and the solvent was evaporated. The residue was crystallized from methanol (50 mL) and water (15 mL), cooled to 0 ° C. and filtered off to give 23.4 g of white crystals. A 3.6 g second harvest was obtained from the parent liquid (27.0 g, 71%): MS-EI ⁺ m / z 286; C _l2 H _l8 N ₂ 0 ₄ S analysis of the theoretical value (measured value):. C 50.3 (50.5) % H 6. 3 (6.2)% N 9.8 (9.7)% S 11.2 (11.2).
[770] Intermediate 2
[771] tert-butyl 4- (2-hydroxyethyl) -1,3-thiazol-2-ylcarbamate
[772] Intermediate 1 (28.6 g, 100 mmol) was dissolved in dry DME (200 mL) and heated to 50 ° C. Lithium borohydride (1.76 g, 81 mmol) was added carefully and the solution heated to 80 ° C. (reflux). After 2 hours, the solution was cooled and acetic acid (15 mL) was carefully added followed by sodium chloride solution. The organic phase is separated and the water solution is extracted three times with ethyl acetate. Combine the organic phases and evaporate the solvent. To destroy the formed boron complex of product alcohol, the residue was dissolved in ethanol (100 mL) and ethanolamine (6.1 g) and refluxed for 30 minutes. The solvent was evaporated and the residue was redissolved in toluene and washed with sodium hydrogen sulfate solution, sodium chloride solution, sodium bicarbonate solution, brine and finally dried over magnesium sulfate. Filtration and solvent removal give a colorless oil in near quantitative yield. : MS-EI ⁺ m / z 244.
[773] Intermediate 3
[774] tert-butyl4- {2-[(2-hydroxyethyl) amino] ethyl} -1,3-thiazol-2-ylcarbamate oxalate
[775] Intermediate 2 (27.5 g, 98 mmol) was dissolved in toluene (150 mL) and cooled to below 5 ° C. TEA (15.0 g, 147 mmol) and mesyl chloride (12.4 g, 125 mmol) were added dropwise at <5 ° C. After 30 minutes, cold water was added and the organic phase was washed with sodium hydrogen sulfate solution, water and sodium hydrogen carbonate solution, then it was dried over magnesium sulfate and the solvent was evaporated. [ ^l H NMR (CDC1 ₃ ) δ 1.50 (s, 9H), 2.87 (s, 3H), 3.13 (t, 2H), 4.43 (t, 2H), 5.26 (s, 1H), 6.62 (s, 1H) ]. The residue was dissolved in ethanolamine (60.4 g, 98 mmol) and kept at 60 ° C. for 2 hours. Ethanolamine was distilled at 60 ° C. and 0.5 Torr. Water was added to the residue and it was extracted with ethyl acetate. The organic phase was washed with water, dried over sodium sulfate and concentrated to dryness. The remaining oil was dissolved in ethanol (100 mL). Heated to 50 ° C. and treated with oxalic acid (9.0 g) in warm ethanol. After cooling the product crystallized out of solution. Ethyl acetate (50 mL) was added and the product collected into a filter and washed with ethyl acetate. 27.8 g (74%) of white crystals were obtained in the process. Analyzes for C ₁₂ H ₂₁ N ₃ O ₃ S. Theoretic (actual): C 44.6 (44.1)% H 6.1 (5.8)% N 11. 1 (11.1)% S 8. 5 (8.4).
[776] Intermediate 4
[777] tert-butyl 4- {2-[(chloroacetyl) (2-hydroxyethyl) amino] ethyl} -1,3-thiazol-2-ylcarbamate
[778] Intermediate 3 (37.7 g, 100 mmol) was dissolved in THF (50 mL) and water (100 mL). To it was added a solution of calcium chloride dihydrate (16.7 g, 110 mmol) in water (15 mL) with the addition of sodium hydroxide solution while maintaining the pH near neutral. The solution was cooled below 10 ° C. and chloroacetyl chloride was added while maintaining the pH at 7-9 with the addition of sodium hydroxide solution. The reaction was terminated when less than 2 equivalents of chloroacetyl chloride was added (TLC). Water and sodium hydrogen sulfate were added and the crude product was extracted with ethyl acetate. The organic phase was washed with water and the solvent was evaporated. The residue was dissolved in toluene and the solution was washed with sodium hydrogen carbonate solution, brine, treated with activated carbon and dried over magnesium sulfate. After evaporation of the solvent 38.5 g (96%) of oil remained: ¹ H NMR (CDC1 ₃ ) δ 1.50 (s, 9H), 2.84 (t, 2H), 3.36 (t, 2H), 3.56 (t, 2H), 3.61 (t, 2H), 4.28 (br s, 2H), 6.73 (s, 1H).
[779] Intermediate 5
[780] tert-butyl 4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-ylcarbamate
[781] A solution of intermediate 4 (8.2 g, 22.5 mmol) in THF (30 mL) was added to aqueous potassium hydroxide (3.6 g in 3.6 mL water, 0.6 mol) while maintaining the temperature at 20-25 ° C. in an ice bath. . After 20 minutes, acetic acid was added and THF was evaporated and the residue was extracted with toluene and washed with sodium hydrogen sulfate and sodium hydrogen carbonate. The organic phase was dried over magnesium sulfate and the solvent was evaporated. The product crystallized in the flask was recrystallized from MTBE to give 4.2 g (57%) of a white solid: ^l H NMR (CDCl ₃ ) δ 1.52 (s, 9H), 2.96 (t, 2H), 3.18 (t, 2H), 3.66 (t, 2H), 3.75 (t, 2H), 4.12 (s, 2H), 6.57 (s, 1H).
[782] Intermediate 6
[783] 4- [2- (2-amino-1,3-thiazol-4-yl) ethyl] -3-morpholinone
[784] The title compound was prepared by stirring Intermediate 5 (145 mg, 0.44 mmol) in DCM and trifluoroacetic acid (1: 1; 5 mL) for 40 minutes. After the solvent was removed and dried in vacuo at 50 ° C. for 18 hours, 105 mg of material was isolated. A portion of this material (55 mg) was dissolved in DCM (7 mL) and washed with aqueous sodium hydroxide (2 M, 1.5 mL), dried over magnesium sulfate and the solvent removed. The white solid was isolated (27 mg, 95% pure by HPLC): ¹ H NMR (CDC1 ₃ ) δ 8.70 (s, 1 H), 6.27 (s, 1 H), 3.95 (s, 2 H), 3.90 ( t, 2H), 3.75 (t, 2H), 3.43 (t, 2H), 2.9 (t, 2H); LCMS (pos) m / z 228.2.
[785] Intermediate 7
[786] tert-butyl (3R) -3-methyl-1-piperazinecarboxylate
[787] R-(-)-2-methylpiperazine (1.00 g, 10 mmol) was dissolved in 50% aqueous methanol (5 mL). Acetic acid (0.57 mL, 10 mmol) was added and the solution cooled on ice. Di-tert-butyldicarbonate (2.18 g, 10 mmol) dissolved in methanol (5 mL) was added slowly. The mixture was allowed to reach room temperature and left for 0.5 hours after gas evolution ceased. The mixture was concentrated in vacuo and a small amount of precipitate (0.1 g) was filtered off. Aqueous potassium carbonate (10 mL, 1M) was added to the filtrate and the solution extracted with ethyl acetate (2 x 20 mL). The organic phase was washed with brine, dried (magnesium sulfate), filtered and evaporated to give 1.68 g (84%) product as a white solid: ¹ H NMR (CDC1 ₃ ) δ 3. 88 (bs, 2H), 2.89 (m, 1H), 2.4-2.8 (m, 3H), 2.3 (m, 1H), 1.62 (1H), 1.41 (s, 9H), 1.0 (d, 3H).
[788] Intermediate 8
[789] 2- (2-amino-1, 3-thiazol-4-yl) -N-ethyl-N-methylacetamide
[790] This compound is 2-amino-4-thiazole acetic acid (3.48 g, 22 mmol), EDCI (4.37 g, 22.8 mmol), DMAP (270 mg, 2.2 mmol) and N-ethylmethylamine (1.99 mL) in DMF (30 mL). , 23.2 mmol). The resulting solution was left at room temperature overnight. DMF was removed in vacuo and the residue was purified by flash chromatography on silica gel using 2% and 5% methanol / ethyl acetate as eluent. This process yielded 2.09 g (40%) of the title compound: ¹ H NMR (CDC1 ₃ ) δ 6.28,6.30 (1H), 5.06 (bs, 1H), 3.60,3.61 (2H), 3.41 (m, 2H ), 3.0,2.92 (s, 3H), 1. 11 (q, 3H). MSEI m / z 200. 2.
[791] Intermediate 9
[792] 2- (2-amino-1, 3-thiazol-4-yl) -N-isopropyl-N-methylacetamide
[793] This compound was prepared as described for Intermediate 8 using N-methyl N-isopropylamine. Yield 0.87 g, 19%: ¹ H NMR (CDC1 ₃ ) δ 6.24 (s, 1H), 4.88,4.20 (m, 1H), 3.64,3.58 (s, 2H), 2.82, 2.77 (s, 3H), 1.08 (t, 6H). MS-ES (pos) m / z 214.2.
[794] Intermediate 10
[795] 4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-amine
[796] This compound was prepared as described for Intermediate 8 using morpholine. DMF was distilled in vacuo and methanol (10 mL) was added to the residue. The mixture was centrifuged and the supernatant was separated. The solid was stirred with methanol (20 mL) and diethyl ether (20 mL). The mixture was centrifuged and the solid was dried in vacuo. Yield 3.19 g, 64%: ^l H NMR (CDC1 ₃ ) δ 6.28 (s, 1H), 5.19 (bs, 3H), 3.5-3.7 (m, 10H). MS-ES (pos) m / z 228.0.
[797] Intermediate 11
[798] 2- (2-amino-1,3-thiazol-4-yl) -N, N-diethylacetamide
[799] This compound was prepared as described for Intermediate 8 using N, N-diethylamine. DMF was distilled off and the residue was recrystallized from methanol. Yield 1.87 g, 40%: ¹ H NMR (DMSO) δ 6.85 (bs, 2H), 6.17 (s, 1H), 3.41 (s, 2H), 3.34 (q, 2H), 3.23 (q, 2H), 1.04 (t, 3H), 0.92 (t, 3H). MS-ES (pos) m / z 214.2.
[800] Intermediate 12
[801] 4- [2-oxo-2- (4-thiomorpholinyl) ethyl J-1,3-thiazol-2-amine
[802] This compound was prepared as described for Intermediate 8 using thiomorpholine. Yield 2.57 g, 48%: ^l H NMR (CDC1 ₃ ) δ 6.28 (s, 1H), 5.25 (bs), 3.7-395 (m, 4H), 2.4-2.65 (m, 4H). MS-ES (pos) m / z 244.2.
[803] Intermediate 13
[804] 4- [2-oxo-2- (1-piperidinyl) ethyll-1,3-thiazol-2-amine
[805] This compound was prepared as described for Intermediate 8 using piperidine. Yield 3.47 g, 70%. ¹ H NMR (CDC1 ₃ ) δ 6.26 (s, 1H), 5.25 (bs, 2H), 3.62 (s, 2H), 3.55 (t, 2H), 3.42 (m, 2H), 1.4-1.66 (6H). MS-ES (pos) m / z 226.2.
[806] Intermediate 14
[807] 2- (2-amino-1,3-thiazol-4-yl) -N, N-diisopropylacetamide
[808] This compound was prepared as described for Intermediate 8 using N, N diisopropylamine. Yield 1. 40 g, 26%: ¹ H NMR (CDC1 ₃ ) δ 6.25 (s, 1H), 5.20 (bs, 2H), 4.01 (m, 1H), 3.58 (s, 2H), 3. 39 (m , 1H), 1.39 (d, 6H), 1.11 (d, 6H). MS-EI ⁺ m / z 241.
[809] Intermediate 15
[810] 2- (2-amino-1,3-thiazol-4-yl) -N, N-dipropylacetamide
[811] This compound was prepared as described for Intermediate 8 using N, N-dipropylamine. Yield 346 mg, 65%: ¹ H NMR (CDC1 ₃ ) δ 6.29 (s, 1H), 5.16 (bs, 2H), 3.61 (s, 2H), 3.25 (m, 4H), 1.56 (m, 4H), 0.88 (m, 6 H). MS-ES (pos) m / z 242.0.
[812] Intermediate 16
[813] 5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-ylamine
[814] A suspension of aluminum chloride (0.86 g, 6.44 mmol) in DCM (50 mL) was treated dropwise with morpholine (4.7 mL, 53.7 mmol) to give a colorless solution. After 1 hour of addition of methyl (2-amino-5-methyl-1,3-thiazol-4-yl) acetate (1.0 g, 5.37 mmol) (orange solution), the reaction mixture was quenched with aqueous citric acid (3%, 10 quenched) and basified with saturated aqueous sodium bicarbonate. Extraction with DCM (3 × 50 mL), the combined organic layers were dried (sodium sulfate) and the volatiles were evaporated to yield 0.70 g of yellow foam. To give ivory solid in DCM / methanol to give a solid (10/1 v / v) flash column chromatography over silica gel eluting with 545mg (42%):. Analysis C ₁₀ for the theoretical value (measured value) H _l5 N ₃ 0 ₂ S: C 49.7 (49.5)% H 6. 3 (6.3)% N 17. 4 (17.3)% S 13. 3 (13.3).
[815] Intermediate 17
[816] 4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-amine
[817] To intermediate 2 (2.12 g, 8.68 mmol) dissolved in pyridine (20 mL) was added methane sulfonyl chloride (1.49 g, 13.02 mmol) at 0 ° C. The mixture is stirred for 4 h at 0 ° C. and then poured into a mixture of ice (37 g) and concentrated HC1 (29 mL). Extraction with ethyl acetate followed by evaporation of the solvent yielded 2.83 g crude mesylate. The crude product was dissolved in ethanol (15 mL) and morpholine (3.02 g, 34.71 mmol) was added. After 3 hours at reflux, all mesylate was converted to an amine and the Boc-group was removed by addition of concentrated HC1 (10 mL). Deprotection was continued at 50 ° C. for 6 hours and the solvent was evaporated. The crude material was purified by reverse phase flash chromatography on LiChroprep RP-18. The product was eluted gradient with (acetonitrile / 0.4% concentrated HCl in H ₂ O). The pure portion was pooled and the solvent volume was reduced by approximately 50% by evaporation. 11M NaOH was added until the product solidified. The solid was filtered off and washed with water (1.04 g, 4.89 mmol, 56%) to give: ¹ H NMR (CD ₃ 0D) δ 2.50 (m, 4H), 2.53 (m, 4H), 3.54 (t, 4H) , 6.19 (s, 1 H); MS (ion spray, [M + H] &lt; + &gt;) m / z 213. Analyzes for C ₉ H _l5 N ₃ 0S. Theoretical values: found C 50.7 (50.5)% H 7.1 (7.3)% N 19.7 (19.8) %.
[818] Intermediate 18
[819] 4-iodo-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
[820] The title compound was prepared according to Method B from Intermediate 10 and pipsyl chloride. The product was purified by dissolving impurities in hot ethanol. Yield 6.39 g, 59%: ¹ H NMR (DMSO) δ 7.91 (d, 2H), 7.55 (d, 2H), 6.52 (s, 1H), 3.64 (s, 2H), 3.4-3.6 (m). MS-ES (neg) m / z 492.3.
[821] Intermediate 19
[822] 4- (chloromethyl) -1,3-thiazol-2-ylamine hydrochloride
[823] A solution of 1,3-dichloroacetone (25.4 g, 200 mmol) in acetone (100 mL) was stirred while dropping a solution of thiourea (15.2 g, 200 mmol) in acetone (500 mL) at a fairly fast rate. . The clear oil began to separate when the addition was about 1/4 complete. The mixture was left overnight during the time the oil solidified to the mass of white crystals. After acetone was poured still, the solid was stirred with EtOH (200 mL). Insoluble material was filtered off and petroleum ether was added to the solution. The product was isolated as an oil and solidified. (18 g, 49%): MS (ion spray, [M + H] ⁺ ) m / z 148. Analyzed for C ₄ H ₅ ClN ₂ S · 1 HC1. Found): C 26.0 (26.0)% H 3.3 (3.2)% N 15.1 (15.1)%.
[824] Intermediate 20
[825] 2-{((2-amino-1, 3-thiazol-4-yl) methyl] amino} ethanol dihydrochloride
[826] Intermediate 19 (1.00 g, 5.40 mmol) was added in portions to 2-ethanolamine (8. 28 g, 135 mmol) and the mixture was stirred at rt overnight. Most of the ethanolamine was evaporated in a rotary evaporator at 100 ° C. and the residue was flash chromatographed on RP silica gel eluting with 5% acetonitrile in H ₂ 0/1% concentrated HC1 to give 790 mg (59%) of oil. . ¹ H NMR (DMSO) δ 2.62 (t, 2H), 3.46 (t, 2H), 6.28 (s, 1H), 6.81 (br s, 1H); MS (ion spray, [M + H] &lt; + &gt;) m / z 174.
[827] Intermediate 21
[828] 4-[(2-amino-1,3-thiazol-4-yl) methyl] -3-morpholinone
[829] To a solution of intermediate 20 (350 mg, 1.42 mmol) in H20 (3 mL) / THF (1.5 mL) was added dropwise chloroacetyl chloride (400 mg, 3.55 mmol) in THF (3 mL) over a period of 20 minutes. The temperature was maintained at 8 ° C. and the pH adjusted to 6-8 by successive addition of aqueous KOH (2 M). Aqueous KOH (6 M, 1.2 mL, 7.2 mmol) was added and the mixture was stirred at rt for 20 min. The pH was adjusted to 8 and the mixture was extracted with ethyl acetate. The organic phase was separated and the solvent was evaporated to give a solid. The solid was boiled in ethyl acetate and then filtered (160 mg, 53%). : ¹ H NMR (DMSO) δ 3.32 (t, 2H), 3.81 (t, 2H), 4.03 (s, 2H), 4.32 (s, 2H), 6.31 (s, lH), 6.81 (brs, 1H); MS (ion spray, [M + H] &lt; + &gt;) m / z 213. Analysis for C ₈ H ₁₁ N ₃ 0 ₂ S. Theoretical value: found C 45.1 (44.9)% H 5.2 (5.4)% N 19. 7 (19.1)%.
[830] Intermediate 22
[831] Tert-butyl 4- [2- (3-oxo-1,4-oxazepan-4-yl) ethyl-1,3-thiazol-2-ylcarbamate
[832] The title compound was prepared starting with Intermediate 2 following essentially the synthetic route outlined in Intermediate 5 and using 3-amino-1 propanol instead of 2-aminoethanol. The product was obtained as an oil after the last step (0.133 g, 86%): ¹ H NMR (DMSO-d ₆ ) δ 11.37 (s, 1 H), 6.78 (s, 1 H), 4.08 (s, 2H), 3.72 (t, 2H), 3. 55 (t, 2H), 3.42 (m, 2H), 2.72 (t, 2H), 1.72 (m, 2H), 1.47 (s, 9H); HRMS theoretical for C ₁₅ H ₂₃ N ₃ 0 ₄ S (found) m / z 341. 1409 (341.1399).
[833] Intermediate 23
[834] Methyl 2- [2- (2-amino-1, 3-thiazol-4-yl) ethoxy] benzoate
[835] Ethyl 2-aminothiazole-4-acetate (931 mg, 5.0 mmol) was dissolved in DCM (10 mL) and TEA (0.765 mL, 5.5 mmol). Trityl chloride (1.53 g, 5.5 mmol) was added in portions. The mixture was left at room temperature overnight and filtered. The filtrate was evaporated and the product was purified by flash-chromatography on silica gel using 20% ethyl acetate / toluene as eluent: ¹ H NMR (CDC1 ₃ ) δ 7.2-7.4 (m), 6.6 (s, 1H ), 6.15 (s, 1H), 4.2 (q, 2H), 3.5 (s, 2H), 1.3 (t, 3H). A solution of tritylated ethyl ester (5 mmol) in THF (18 mL) was added to lithium aluminum borohydride (1.00 g, 26 mmol) in THF (100 mL) while cooling on ice. The mixture was stirred at rt overnight and then cooled on ice. Aqueous sodium hydroxide (10%, 15 mL) was added carefully. The solution was separated from the precipitate. The precipitate was washed with THF and ethyl acetate. The combined solution was evaporated and the residue was dissolved in ethyl acetate (80 mL) and washed with brine. Evaporation and chromatography on silica gel with 20% and 50% ethyl acetate in toluene gave 1.22 g product, 63% yield: ¹ H NMR (CDC1 ₃ ) δ 7.2-7.4 (m), 6.4 (s, 1H) , 6.0 (s, 1H), 3.75 (t, 2H), 2.7 (t, 2H). This material (386 mg, 1.0 mmol), methyl salicylate (183 mg, 1.2 mmol) and triphenylphosphine (314 mg, 1.2 mmol) were dissolved in THF (5 mL). N, N, N'N'-tetramethylazo-dicarboxamide (206 mg, 1.2 mmol) was added and the solution was left overnight. The mixture was filtered and the filtrate was purified by flash-chromatography on silica gel using toluene and ethyl acetate / toluene as eluent. Yield 418 mg, 80%: ¹ H NMR (CDC1 ₃ ) δ 7.74 (d, 1H), 7.4 (m, 1H), 7.18-7.38 (m), 6.95 (m, 2H), 6.5 (s, 1H), 6.15 (s, 1H), 4.2 (q, 2H), 3.8 (s, 3H), 3.0 (t, 2H). MS-ES (pos) m / z 521.2. Methyl 2- {2- [2- (tritylamino) -1,3-thiazol-4-yl] ethoxy} benzoate (343 mg, 0.656 mmol) was added methanol: concentrated HCl 9: 1 (50 mL) and Mix and heat to 60 ° C. for 24 h. The mixture was concentrated to 10 mL, filtered and the filtrate was made alkaline with aqueous sodium carbonate (1 M). The solution was extracted with chloroform. Evaporation gave the product, which was purified by flash-chromatography on silica gel using 0-2% methanol / DCM as eluent. Yield 128 mg, 70% (partially crystalline): ^l H NMR (CDC1 ₃ ) δ 7.75 (d, 1H), 7.42 (t, 1H), 6.96 (m, 2H), 6.35 (s, 1H), 4.29 (t , 2H), 3.85 (s, 3H), 3.05 (t, 2H). MS-ES (pos) m / z 279.3.
[836] Known examples
[837] The compounds of these examples are all commercially available and can be purchased, for example, from Kalamazoo.
[838] 1A ethyl (2-{[(2, 4-dichloro-5-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[839] 2A ethyl (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[840] 3A ethyl (2-{[(4-chloro-2, 5-dimethylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[841] 4A ethyl (2- {[(2, 4-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[842] 15A ethyl (2-{[(3-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[843] 20A ethyl {2-[(phenylsulfonyl) amino] -1,3-thiazol-4-yl} acetate
[844] New embodiments
[845] The following specific compounds were synthesized. Commercially available compounds thus form embodiments only with the use of such compounds and pharmaceutical agents as set forth in the appended claims, as indicated above in the specification.
[846] Example 5A
[847] Ethyl 2- (2-(((4-methylphenyl) sulfonyl) amino) -1,3-thiazol-4-yl) acetate
[848] The title compound was prepared according to Method A from ethyl 2-amino-4-thiazolylacetate and 4methylbenzenesulfonyl chloride to give 0.36 g (66%) of a pink solid; mp 173 ° C; MS (ion spray, [M + H] ⁺ ) m / z 341.
[849] Example 6A
[850] Ethyl 2- (2-{[(2, 5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[851] The title compound was prepared according to Method A from ethyl 2-amino-4-thiazolylacetate and 2,5-dichloro-3-thienyl) sulfonyl chloride to give 0.44 g (70%) of a red solid: MS ( Ion spray, [M + H] ⁺ ) m / z 400; C ₁₁ H ₁₀ Cl ₂ N ₂ 0 ₄ S ₃ .0. 7 Analysis for HC1. Theoretical (actual): C 31.0 (31.0)%, H 2.2 (2.2)%, N 6.6 (6.8)%.
[852] Example 7A
[853] Ethyl (2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[854] The title compound was prepared according to Method A from ethyl 2-amino-4-thiazolylacetate and 2-chlorobenzenesulfonyl chloride to give 0.65 g (22%) of a pink solid after recrystallization from methanol: MS (ion Spray, [M + H] ⁺ ) m / z 361; Analysis of C ₁₃ H ₁₃ ClN ₂ 0 ₄ S _2. Theoretic (actual): C 43.3 (43.2)%, H 3.6 (3.5)%, N 7.8 (7.6)%.
[855] Example 8A
[856] Ethyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[857] The title compound was prepared using Quest 210 equipment at 30 ° C. according to Method A from ethyl 2-amino-4-thiazolylacetate and 3-chloro-2-methylbenzenesulfonyl chloride. This procedure gave 2.05 g (34%) of a grayish white solid: mp 154 ° C.; MS (ion spray, [M + H] ⁺ ) m / z 375; Analysis of C ₁₄ H ₁₅ ClN ₂ O ₄ S _2. Theoretic (actual): C 44.9 (45.0)%, H 4.0 (3.7)%, N 7.5 (7.1)%.
[858] Example 10A
[859] Ethyl 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} acetate
[860] The title compound was prepared at 30 ° C. using ethyl 2-amino-4-thiazolylacetate and 1,1′-biphenylsulfonyl chloride Quest 210 equipment to obtain 0.99 g (23%) of a grayish white solid. mp 182 ° C .; MS (ion spray, [M + H] &lt; + &gt;) m / z 403; Analyzes for C ₁₉ H ₁₈ N ₂ 0 ₄ S ₂ .0.1 H ₂ 0. Theoretical value: found C 56.4 (56.6)%, H 4.5 (4.3)%, N 6.9 (6.3)%.
[861] Example 12A
[862] Ethyl 2- (2-{[(3-bromophenyl) sulfonyl] amino} -1, 3-thiazol-4-yl) acetate
[863] According to Method A, the title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3-bromobenzenesulfonyl chloride at 30 ° C. using a Quest 210 instrument, with 1.16 g (27%) of grayish color. A white solid was obtained: mp 155 ° C; MS (ion spray, [M + H] ⁺ ) m / z 405; Anal for C ₁₃ H ₁₃ BrN ₂ 0 ₄ S _2. Theoretical values: found C 38.5 (38.4)%, H 3.2 (3.0)%, N 6.9 (6.6)%.
[864] Example 13 A
[865] Ethyl (2-{[(4-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[866] According to Method A, the title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-nitrobenzenesulfonyl chloride, and 8.66 g (46%) of the product were obtained: MS (ion spray, [M + H] ] ⁺ ) m / z 372; C _l3 H _l3 N ₃ 0 ₆ S ₂ Analysis of the theoretical value (measured value):. C 42.0 (42.5) % H 3. 5 (3.3)% N 11. 3 (11. 4)%.
[867] Example 14A
[868] Ethyl (2-{[(4-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[869] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-methoxybenzenesulfonyl chloride according to Method A, and 9.83 g (55%) of pure material was obtained: MS (ion spray, [M + H] +) m / z 356; _{Anal for} C ₁₄ H ₁₆ N ₂ 0 ₅ S _2. Theoretic (act): C 47.2 (47.1)% H 4.5 (4.5)% N 7.9 (7.8)%.
[870] Example 16A
[871] Ethyl (2-{[(3-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[872] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3-methylbenzenesulfonyl chloride according to Method A, giving 0.51 g (75%) of pink powder: MS (Electrospray, [MH] ⁻ m / z 339.2.
[873] Example 17A
[874] Ethyl (2- {1 (3-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[875] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3chlorobenzenesulfonyl chloride according to Method A, yielding 0.47 g (65%) of pink powder: MS (Electrospray, [MH] ^- ) m / z 359.1.
[876] Example 18A
[877] Ethyl (2-{[(4-fluorophenyl) sulfonyl} amino 1-1,3-thiazol-4-yl) acetate
[878] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4fluorobenzenesulfonyl chloride according to Method A, and 0.29 g (42%) of pink powder was obtained: MS (Electrospray, [MH] ^- ) m / z 343.1
[879] Example 19A
[880] Ethyl (2-{[(3-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[881] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3-fluorobenzenesulfonyl chloride according to Method A, and 0.55 g (80%) of pink powder was obtained: MS (Electrospray, [MH]). -) m / z 343.1
[882] Example 21A
[883] Ethyl (2-{[(4-isopropylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[884] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4 isopropylbenzenesulfonyl chloride according to Method A, and 0.57 g (78%) of pink powder was obtained: MS (Electrospray, [MH]- ) m / z 367.2.
[885] Example 22A
[886] Ethyl [2-({[3-({l4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino) -1 , 3-thiazol-4-yl] acetate
[887] Synthesis Method A was carried out with ethyl-2-amino-4-thiazole acetate (0.37 g, 2 mmol), 3-carboxylphenylsulfonyl chloride (0.49 g, 2.2 mmol), and pyridine (10 mL). . Purification gave the title compound as a cream powder (52 mg, 7%): MS (Electrospray, [M-H]-) m / z 537.2.
[888] Example 23A
[889] Ethyl [2-({[4-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino)- 1,3-thiazol-4-yl] acetate
[890] Synthesis Method A was carried out with ethyl-2-amino-4-thiazole acetate (0.37 g, 2 mmol), 4-carboxyphenylsulfonyl chloride (0.49 g, 2.2 mmol), and pyridine (10 mL). . Purification gave the title compound as a cream powder (44 mg, 6%): MS (Electrospray, [MH] ⁻ ) m / z 537. 2.
[891] Example 24A
[892] Ethyl (2-{[(2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[893] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2 methylbenzenesulfonyl chloride according to Method A, giving 0.22 g (32%) of pink powder: ¹ H NMR (CDC1 ₃ ) δ: 1.3 (3H, t), 2.5 (3H, s), 3.9 (2H, s), 4. 2 (2H, q), 6. 4 (1H, s), 7.8-7.2 (3H, m), 8.1 (1H , t).
[894] Example 25A
[895] Ethyl [2-({[2- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[896] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2-trifluoromethylbenzenesulfonyl chloride according to Method A, and 0.13 g (31%) after recrystallization from acetone / ether / petroleum ether A red solid was obtained. : mp 171 ° C; MS (ion spray, [M + H] ⁺ ) m / z 395; Analysis of C ₁₄ H ₁₃ F ₃ N ₂ 0 ₄ S _2. Theoretic (actual): C 42.6 (43.0)%, H 3.3 (2.9)%, N 7.1 (6.9)%.
[897] Example 26A
[898] Ethyl [2-({[3- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[899] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3trifluoromethylbenzenesulfonyl chloride according to Method A, and after 0.26 g (62%) of recrystallization from acetone / ether / petroleum ether An orange solid was obtained: mp 145 ° C.; MS (ion spray, [M + H] &lt; + &gt;) m / z 395; Analysis for C ₁₄ H _l3 F ₃ N ₂ 0 ₄ S _2. Theoretical values: found C 42.6 (42.8)%, H 3.3 (2.9)%, N 7.1 (6.9)%
[900] Example 27A
[901] Ethyl [2-({[4- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[902] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4trifluoromethylbenzenesulfonyl chloride according to Method A, and after recrystallization from acetone / ether / petroleum ether, 0.14 g (33%) of A grayish white solid was obtained: mp 174 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 395; Analysis of C ₁₄ H _l3 F ₃ N ₂ 0 ₄ S _2. Theoretic (actual): C 42.6 (42.4)%, H 3.3 (2.8)%, N 7.1 (6.8)%
[903] Example 28A
[904] Ethyl 2- (2-{[(4-bromophenyl) sulfonyl] amino) -1,3-thiazol-4-yl) acetate
[905] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-bromobenzenesulfonyl chloride according to Method A and 0.14 g (31%) of pink after recrystallization from acetone / ether / petroleum ether A solid was obtained: mp 183 ° C.; MS (ion spray, [M + H] &lt; + &gt;) m / z 405; Analyzes for C ₁₃ H ₁₃ BrN ₂ 0 ₄ S _2. Theoretic (actual): C 38.5 (38.5)%, H 3.2 (3.0)%, N 6.9 (6.6)%
[906] Example 29A
[907] Ethyl (2-{[(2-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[908] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2-nitrobenzenesulfonyl chloride as described in Synthesis Method B. The reaction mixture was applied over a Hydromatrix column pretreated with aqueous HC1 (0.5 mL, 2 M) and eluted with DCM. After concentration the material was purified by preparative LCMS and lyophilized to give a white solid (26.6 mg) with purity> 90%: ¹ H-NMR (DMSO-d ₆ ) δ 11.40 (s, NH), 8.24 (m, 1H ), 7.65 (m, 3H), 6.39 (s, 1H), 4.21 (dd, J = 7.2 Hz, J = 14.4 Hz, 2H), 3.73 (s, 2H), 1.28 (t, J = 7.2 Hz, 3H ); HRMS calcd for C ₁₃ H ₁₃ N ₃ 0 ₆ S ₂ m / z 371.0246 (371.0248).
[909] Example 30A
[910] Ethyl (2-{[(2,4-dichloro-6-methylphenylsulfonyl] amino} -1,3-thiazol-4-yl) acetate
[911] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,4-dichloro-6-methylbenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (34.6 mg) having a purity> 90%. ) Was obtained: LCMS (pos) m / z 409, 411.0; HRMS m / z 407.9753 (Theoretical value of single isotope mass for C ₁₄ H ₁₄ Cl ₂ N ₂ 0 ₄ S ₂ is 407.9772).
[912] Example 31A
[913] Ethyl (2-{[(2, 4, 6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[914] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,4,6-trichlorobenzenesulfonyl chloride as described in Synthesis Method B, white solid (32.0 mg) with purity> 90%. Obtained: LCMS (pos) m / z 431 .0; HRMS m / z 427.9238 (Theoretical value of single isotope mass for C ₁₃ H _ll Cl ₃ N ₂ 0 ₄ S ₂ is 427.9226).
[915] Example 32A
[916] Ethyl (2-{[(2,4-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[917] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,4-dichlorobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (45.8 mg) with a purity> 90%. MS (pos) m / z 395.2, 397.2.
[918] Example 33A
[919] Ethyl (2-{[(5-fluoro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[920] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 5-fluoro-2-methylbenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (32.7 mg) with a purity> 90%. Got. LCMS (pos) m / z 359.2.
[921] Example 34A
[922] Ethyl (2-{[(4-propylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) acetate
[923] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-n-propylbenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (16.0 mg) with purity> 90%. LCMS (pos) m / z 369.0.
[924] Example 35A
[925] Ethyl (2-{[(2-methoxy-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[926] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2-methoxy-4-methylbenzenesulfonyl chloride as described in Synthesis Method B, white solid (2.3 mg) with purity> 90%. Got. LCMS (pos) m / z 371. 2.
[927] Example 36A
[928] Ethyl (2-{[(3,5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[929] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3,5-dichlorobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (42.2 mg) with purity> 90%. LCMS (pos) m / z 395.0, 397.0.
[930] Example 37A
[931] Ethyl [2-({[4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[932] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4- (3-chloro-2-cyanophenoxy) benzenesulfonyl chloride as described in Synthesis Method B, having a purity> 90%. A white solid (41.4 mg) was obtained. LCMS (pos) m / z 478.0.
[933] Example 38A
[934] Ethyl (2-{[(3,4-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[935] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3,4-dichlorobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (50.1 mg) with a purity> 90%. LCMS (pos) m / z 395.0, 397.0.
[936] Example 39A
[937] Ethyl (2-{[(4-butoxyphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) acetate
[938] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-n-butoxybenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (11.8 mg) with purity> 90%. . LCMS (pos) m / z 399. 2.
[939] Example 40A
[940] Ethyl (2-{[(4-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[941] White-yellow solid (9.4 mg) with purity> 90% prepared as title compound from ethyl 2-amino-4-thiazolylacetate and 4-chloro-2-methylbenzenesulfonyl chloride as described in Synthesis Method B Got. LCMS (pos) m / z 375.2.
[942] Example 41A
[943] Ethyl [2-({[4- (acetylamino) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[944] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-acetamidobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (5.6 mg) having a purity> 90%. LCMS (pos) m / z 384.2.
[945] Example 42A
[946] Ethyl {2-[(8-quinolinylsulfonyl) amino] -1,3-thiazol-4-yl} acetate
[947] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 8 quinolinesulfonyl chloride as described in Synthesis Method B to give a white yellow solid (9.2 mg) having a purity> 80%. LCMS (pos) m / z 378.2.
[948] Example 43A
[949] Ethyl (2-{[(3,4-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[950] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3,4-dimethoxybenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (19.3 mg) having a purity> 90%. . LCMS (pos) m / z 387. 2.
[951] Example 44A
[952] Ethyl (2-{[(4-iodophenyl) sulfonyl] amino) -1,3-thiazol-4-yl) acetate
[953] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and pipsyl chloride as described in Synthesis Method B to give a white solid (47.0 mg) having a purity> 90%. LCMS (pos) m / z 453.0.
[954] Example 45A
[955] Ethyl (2-{[(3-chloro-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[956] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3-chloro-4-methylbenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (51.7 mg) having a purity> 90%. Got it. LCMS (pos) m / z 375.2.
[957] Example 46A
[958] Ethyl [2-({[5- (dimethylamino) -1-naphthyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[959] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and monoyl chloride as described in Synthesis Method B to give a yellow solid (10.0 mg) with a purity> 90%. LCMS (pos) m / z 420.2.
[960] Example 47A
[961] Ethyl (2-{[(1-methyl-lH-imidazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[962] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 1 methylamidazole-4-sulfonyl chloride as described in Synthesis Method B to give a white solid (3.2 mg) having a purity> 90%. . LCMS (pos) m / z 331. 0.
[963] Example 48A
[964] Ethyl (2-{[(5-bromo-2-methoxyphenyl) sulfonyliamino) -1,3-thiazol-4-yl) acetate
[965] White solid (14.4 mg) with purity> 90% prepared as title compound from ethyl 2-amino-4-thiazolylacetate and 5-bromo-2-methoxybenzenesulfonyl chloride as described in Synthesis Method B Got. LCMS (pos) m / z 437.0.
[966] Example 49A
[967] Ethyl (2-{[(2,5-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[968] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,5-dimethoxybenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (17.0 mg) having a purity> 80%. . LCMS (pos) m / z 387. 2.
[969] Example 50A
[970] Ethyl {2-[(2-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetate
[971] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2-naphthalenesulfonyl chloride as described in Synthesis Method B to give a white solid (41.2 mg) with a purity> 90%. LCMS (pos) m / z 377.2.
[972] Example 51A
[973] Ethyl {2-[(mesitylsulfonyl) amino] -1,3-thiazol-4-yl} acetate
[974] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2-mesitylenesulfonyl chloride as described in Synthesis Method B to give a white-yellow solid (7.5 mg) having a purity> 90%. LCMS (pos) m / z 369. 0.
[975] Example 52A
[976] Ethyl (2-{[(3-bromo-5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[977] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3-bromo-5-chlorothiophen-2-sulfonyl chloride as described in Synthesis Method B to give a yellow solid having a purity> 90%. (29.0 mg) was obtained. MS (pos) m / z 445.0, 447.0.
[978] Example 53A
[979] Ethyl {2-[({5-[(benzoylamino) methyl] -2-thienyl} sulfonyl) amino] -1,3-thiazol-4-yl} acetate
[980] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 5-[(benzoylamino) methyl] thiophene 2-sulfonyl chloride as described in Synthesis Method B, to give a white solid having purity> 70%. (8. 6 mg) was obtained. MS (pos) m / z 466.2.
[981] Example 54A
[982] Ethyl {2-[({5- [1-methyl-5- (trifluoromethyl) -lH-pyrazol-3-yl] -2-thienyl} sulfonyl) amino] -1,3-thiazole -4-yl} acetate
[983] Ethyl 2-amino-4-thiazolylacetate and 2- [1-methyl-5- (trifluoromethyl) pyrazol-3-yl] -thiophen-5-sulfonyl chloride as described in Synthesis Method B The title compound was prepared to give a yellow solid with a purity of 93%. MS (Electrospray, [M + H] &lt; + &gt;) m / z 481.0.
[984] Example 55A
[985] Ethyl (2-{[(4-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[986] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-cyanobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (16.9 mg) with a purity> 90%. MS (pos) m / z 352.2.
[987] Example 56A
[988] Ethyl {2-[({5- [2- (methylsulfanyl) -4-pyrimidinyl] -2-thienyl} sulfonyl) amino] -1,3-thiazol-4-yl} acetate
[989] The title compound is prepared from ethyl 2-amino-4-thiazolylacetate and 5- [2- (methylthio) pyrimidin-4-yl] thiophene-2-sulfonyl chloride as described in Synthesis Method B, A white solid (34.5 mg) was obtained with a purity> 90%. MS (pos) m / z 475.3.
[990] Example 57A
[991] Ethyl (2-{[(3-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[992] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3-cyanobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (39.4 mg) with purity> 90%. MS (pos) m / z 352.3.
[993] Example 59A
[994] Ethyl (2-{(2,4,5-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[995] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,4,5-trichlorobenzenesulfonyl chloride as described in Synthesis Method B, yielding a white solid (51.0 mg) having a purity> 90%. ) MS (pos) m / z 429.0.431.0.
[996] Example 60A
[997] Ethyl [2-({[((E) 2-phenylethenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[998] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and beta-styrenesulfonyl chloride as described in Synthesis Method B to give a white solid (21.3 mg) with a purity> 90%. MS (pos) m / z 353.1.
[999] Example 61A
[1000] Ethyl (2-{[(2,3,4-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1001] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,3,4-trichlorobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (51.9 mg) with a purity> 90%. Got. MS (pos) m / z 429.0,431.0,433.0.
[1002] Example 63A
[1003] Ethyl (2-{[(4-bromo-2,5-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1004] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-bromo-2,5-difluorobenzenesulfonyl chloride as described in Synthesis Method B, to give a white solid having purity> 90%. (21.9 mg) was obtained. MS (pos) m / z 441.0, 443.0.
[1005] Example 64A
[1006] Ethyl [2-({[4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[1007] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4- (trifluoromethoxy) benzenesulfonyl chloride as described in Synthesis Method B, white solid (29.1 mg) with purity> 90%. Got. MS (pos) m / z 411.1.
[1008] Example 65A
[1009] Ethyl (2-{[(2,3-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1010] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,3-dichlorobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (25.0 mg) with a purity> 90%. MS (pos) m / z 395.1, 397.1.
[1011] Example 66A
[1012] Ethyl (2-{[(2-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1013] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2-bromobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (41.9 mg) having a purity> 90%. MS (pos) m / z 405.1, 407.1.
[1014] Example 67A
[1015] Ethyl (2-{[(4,5-dichloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1016] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,3-dichlorothiophen-5-sulfonyl chloride as described in Synthesis Method B to give a white-yellow solid having a purity> 90% ( 36. 9 mg) was obtained. MS (pos) m / z 401. 1, 403.1.
[1017] Example 68A
[1018] Ethyl [2-({[4- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[1019] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-benzenesulfonylthiophen-2-sulfonyl chloride as described in Synthesis Method B, yellow solid (29.5 mg) with purity> 90%. Got. MS (pos) m / z 473.1.
[1020] Example 69A
[1021] Ethyl [2-({(5- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[1022] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 5-phenylthiophen-2, 5-disulfonyl chloride as described in Synthesis Method B, to give a yellow solid (18.5 mg) having a purity> 90%. ) MS (pos) m / z 473.1.
[1023] Example 70A
[1024] Ethyl (2-{[(2,6-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1025] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,6-dichlorobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (32.5 mg) having a purity> 90%. MS (pos) m / z 395.1, 397.1.
[1026] Example 71A
[1027] Ethyl (2-{[(2-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1028] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2-cyanobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (24.6 mg) with purity> 90%. MS (pos) m / z 352. 2.
[1029] Example 72A
[1030] Ethyl [2-({[4- (acetylamino) -3-chlorophenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[1031] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-acetamido-3-chlorobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (16.1 mg) having a purity> 90%. ) MS (pos) m / z 418.2, 420.2.
[1032] Example 73A
[1033] Ethyl (2-{[(5-chloro-1,3-dimethyl-1H-pyrazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1034] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 5-chloro-1,3-dimethylpyrazole-4-sulfonyl chloride as described in Synthesis Method B, white with a purity> 90%. A solid (14.8 mg) was obtained. MS (pos) m / z 397.2, 381.2.
[1035] Example 74A
[1036] Ethyl (2-{[(3-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1037] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3-methoxybenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (18.6 mg) having a purity> 90%. LCMS (pos) m / z 357. 0.
[1038] Example 75A
[1039] Ethyl (2-{[(4-bromo-5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1040] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-bromo-5-chlorothiophen-2-sulfonyl chloride as described in Synthesis Method B to give a white- having a purity> 90%. A yellow solid (40.9 mg) was obtained. MS (pos) m / z 445.0, 447.0.
[1041] Example 76A
[1042] Ethyl 2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetate
[1043] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 1-naphthylsulfonyl chloride according to Method A to afford crude product, which was flash column chromatography on silica gel eluting with 2% methanol in DCM. This gave pure title compound (3.93 g, 89%). MS (ion spray, [M + H] ⁺ ) m / z 376; Anal for C ₁₇ H ₁₆ N ₂ 0 ₄ S _2. Theoretical value: found 54.2 (54.02)% H 4.3 (3.9)% N 7.4 (7.1)%.
[1044] Example 77A
[1045] Ethyl (2-{[(2,5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1046] 0.22 g (27%) of the title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,5-dibenzenesulfonyl chloride according to Method A and recrystallized from acetone / ether / petroleum ether. A pink solid was obtained: mp 171 ° C; MS (ion spray, [M + H] ⁺ ) m / z 395; Analysis for _{C l3 H l2 Cl 2 N 2} O 4 S 2 Calcd (found):. C 39.5 (39.7) %, H 3.1 (2.9)%, N 7.1 (6.8)%.
[1047] Example 77B
[1048] Ethyl [2-({[4- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[1049] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-methylsulfonylbenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (20.9 mg) with a purity> 90%. MS (pos) m / z 405.3.
[1050] Example 77C
[1051] Ethyl [2-({[2- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[1052] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2-methylsulfonylbenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (28.4 mg) having a purity> 90%. MS (pos) m / z 405.4.
[1053] Example 77D
[1054] Ethyl (2-{[(4-bromo-2-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1055] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-bromo-2-fluorobenzenesulfonyl chloride as described in Synthesis Method B, yielding a white solid (15.1 mg) having a purity> 90%. ) MS (pos) m / z 423.3,425.3.
[1056] Example 77F
[1057] Ethyl (2-{[(2, 3, 4-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1058] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,3,4-trifluorobenzenesulfonyl chloride as described in Synthesis Method B, to give a yellow solid (2.3 mg) having a purity> 90%. ) MS (pos) m / z 381.4.
[1059] Example 77G
[1060] Ethyl (2-{[(7-chloro-2, 1,3-benzoxadiazol-4-yl) sulfonyl] amino) -1,3-thiazol-4-yl) acetate
[1061] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-chloro-7-chlorosulfonyl-2, 1,3-benzoxadiazol as described in Synthesis Method B, with a purity> 90%. A yellow solid (2.5 mg) was obtained. MS (pos) m / z 403.4.
[1062] Example 77H
[1063] Ethyl (2-{[(2,4,6-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1064] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,4,6-trifluorobenzenesulfonyl chloride as described in Synthesis Method B to give a yellow solid (1.0 mg) with a purity> 90%. ) MS (pos) m / z 381. 4.
[1065] Example 771
[1066] 2-Chloro-5-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} sulfonyl) -4-fluorobenzoic acid
[1067] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2-chloro-5-chlorosulfonyl-4-fluorobenzoic acid as described in Synthesis Method B to obtain a white solid having a purity> 90% ( 26.5 mg). MS (pos) m / z 421. 4,423.4.
[1068] Example 77J
[1069] Ethyl (2-{[(5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1070] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 5-chlorothiophen-2-sulfonyl chloride as described in Synthesis Method B to give a white solid (24.3 mg) having a purity> 90%. Got it. MS (pos) m / z 367. 1,369.1.
[1071] Example 77K
[1072] Ethyl (2-{[(2-chloro-4-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1073] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2-chloro-4-fluorobenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (13.9 mg) with a purity> 90%. Got. MS (pos) m / z 379. 2,381.2.
[1074] Example 77L
[1075] Ethyl [2-({[5- (3-isoxazolyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[1076] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 5-isoxazol-3-ylthiophene-2-sulfonyl chloride as described in Synthesis Method B, to give a yellow solid having a purity> 90% ( 15.9 mg). MS (pos) m / z 400.3.
[1077] Example 77M
[1078] Ethyl (2-{[(4-bromo-2-methylphenyl) sulfonyl] amino] -1,3-thiazol-4-yl) acetate
[1079] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-bromo-2-methylbenzenesulfonyl chloride as described in Synthesis Method B to give a white solid (48.2 mg) with a purity> 90%. Got. MS (pos) m / z 419.2, 421.2.
[1080] Example 77N
[1081] Ethyl (2-{[(4-phenoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1082] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and [(4-phenoxy) benzene] sulfonyl chloride as described in Synthesis Method B, white solid (33.5 mg) with purity> 90%. Got. MS (pos) m / z 419.3.
[1083] Example 770
[1084] Ethyl (2-{[(4-chloro-2, 6-dimethylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) acetate
[1085] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-chloro-2,6-dimethylbenzenesulfonyl chloride as described in Synthesis Method B, giving a white solid (27.3 mg) having a purity> 90%. ) MS (pos) m / z 389. 3,391.3.
[1086] Example 77P
[1087] Ethyl [2-({[2-methyl-4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate
[1088] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2-methyl-4-trifluoromethoxybenzenesulfonyl chloride as described in Synthesis Method B to give a yellow solid (41.7) having a purity> 90%. mg). MS (pos) m / z 425.3.
[1089] Example 77Q
[1090] Ethyl [2-({[2,4-bis (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl} acetate
[1091] The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,4-ditrifluoromethylbenzenesulfonyl chloride as described in Synthesis Method B, yielding a white solid (61. 0 mg). MS (pos) m / z 463.3.
[1092] Example 78A
[1093] Ethyl 2- {2-[[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] -1,3-thiazol-4-yl} acetate
[1094] To a solution of Example 8A (1.50 g, 4.00 mmol) and N-ethyldiisopropylamine (0.57 g, 4.40 mmol) in DMF (10 mL) was added methyl iodide (0.57 g, 4.00 mmol). The mixture was stirred at rt overnight. The residue was purified by flash column chromatography on silica gel, evaporating the solvent and eluting with DCM. The product was crystallized with DCM / petroleum ether to give 0.11 g (7%) of a white solid: MS (ion spray, [M + H] ⁺ ) m / z 388; C ₁₅ H _l7 ClN ₂ 0 ₄ S ₂ Analysis of the theoretical value (measured value):. C 46.3 (46.5) % H 4.4 (4.6)% N 7.2 (7.2)%.
[1095] Example 79A
[1096] Ethyl oxo (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1097] The title compound was prepared from ethyl (2-amino-4-thiazolyl) glyoxylate and 4-n-propylbenzenesulfonyl chloride as described in Synthesis Method B to give a yellow solid (14.5 mg) having a purity> 90%. ) LCMS (pos) m / z 383.2.
[1098] Example 80A
[1099] Ethyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) (oxo) acetate
[1100] Ethyl (2-amino-4-thiazolyl) glyoxylate and 3-chloro-2-methylbenzenesulfonyl chloride title compound were prepared as described in Synthesis Method B to give a yellow solid (32.5) having a purity> 90%. mg). LCMS (pos) m / z 389.0. B
[1101] Example 81A
[1102] Ethyl oxo (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1103] The title compound was prepared from ethyl (2-amino-4-thiazolyl) glyoxylate and 2,4,6-trichlorobenzenesulfonyl chloride as described in Synthesis Method B to give a yellow solid having a purity> 80%. (18.3 mg) was obtained. LCMS (pos) m / z 445.0.
[1104] Example 82A
[1105] Ethyl {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} (oxo) acetate
[1106] The title compound was prepared from ethyl (2-amino-4-thiazolyl) glyoxylate and 4-phenylbenzenesulfonyl chloride as described in Synthesis Method B to give a yellow solid (28.2 mg) having a purity> 80%. Got it. LCMS (pos) m / z 417.0.
[1107] Example 83A
[1108] Ethyl (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) (oxo) acetate
[1109] The title compound was prepared from ethyl (2-amino-4-thiazolyl) glyoxylate 2,4 dichloro-6-methylbenzenesulfonyl chloride as described in Synthesis Method B, to give a yellow solid having a purity> 90% ( 28.9 mg) was obtained: LCMS (pos) m / z 423; HRMS m / z 421. 9580 (421.9565 the value of the theoretical mass for _{C I4 H l2 C l2 N 2} O 5 S 2).
[1110] Example 84A
[1111] 2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid
[1112] The title compound was prepared from Example 5A according to Method C to give 0.15 g (77%) of a white solid: mp 187 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 313; _{Anal for} C ₁₂ H ₁₂ N ₂ 0 ₄ S _2. Theoretic (actual): C 46.1 (46.1)%, H 3.9 (3. 9)%, N 9.0 (8.9)%.
[1113] Example 85A
[1114] 2- (2-{[(2,5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid
[1115] The title compound was prepared from Example 6A according to Method C to afford 0.41 g (100%) of a pale brown solid: mp 174 ° C .; MS (ion spray, [M + H] &lt; + &gt;) m / z 372; Anal for C ₉ H ₆ Cl ₂ N ₂ 0 ₄ S ₃ .0.8HCl. Theoretic finding: C 26.9 (26.9)%, H 1.7 (1.6)%, N 7.0 (6.6)%.
[1116] Example 86A
[1117] (2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid
[1118] The title compound was prepared from Example 7A according to Method C and obtained 1.49 g (90%) of a pink solid after recrystallization from acetone / ether / petroleum ether: mp176 ° C .; MS (ion spray, [M + H] &lt; + &gt;) m / z 333; Analysis of C ₁₁ H ₉ ClN ₂ O ₄ S _2. Theoretic (act): C 39. 7 (39.4)%, H 2.7 (2.6)%, N 8.4 (8.2)%.
[1119] Example 87A
[1120] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid
[1121] The title compound was prepared according to Example 8A according to Method C, and 1.89 g (100%) of a grayish white solid were obtained: mp 198 ° C .; MS (ion spray, [M + H] &lt; + &gt;) m / z 347; Anal for C ₁₂ H ₁₁ ClN ₂ O ₄ S ₂ .0.9 HCl. Theoretic finding: C 38.0 (38.0)%, H 3.2 (2.6)%, N 7. 4 (7.1)%.
[1122] Example 88A
[1123] Isopropyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1124] Example 87A (0.3 g, 0.9 mmol) in DCM (7 mL) was treated dropwise with oxalyl chloride (0.1 g, 0.9 mmol) and a catalytic amount of DMF. The reaction mixture was stirred for 3 hours. The solvent was removed under reduced pressure and isopropanol was added to the remaining grayish white solid. The resulting suspension was stirred overnight. Purification by flash column chromatography on silica gel eluting with methanol (1->3-> 5%) in DCM gave a pink oil. After crystallization with acetone / petroleum ether analytically pure pink crystals were obtained: mp 114 ° C.; MS (ion spray, [M + H] &lt; + &gt;) m / z 389; _{Anal for} C ₁₅ H ₁₇ CIN ₂ 0 ₄ S _2. Theoretic (act): C 46.3 (46.4)%, H 4.4 (4.2)%, N 7.2 (7.2)%.
[1125] Example 89A
[1126] Phenyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1127] Under N ₂ atmosphere, Example 87A (0.5 g, 1.4 mmol) and DMAP (0.3 g, 1.6 mmol) were dissolved in DCM (40 mL). The resulting red solution was cooled (0 ° C.) before the addition of EDCI (0.3 g, 1.6 mmol) and phenol (0.7 g, 7. 2 mmol). The mixture was warmed to room temperature and stirred overnight. The reaction mixture was washed with aqueous HC1 and pore aqueous sodium bicarbonate. The organic phase was removed and the residue was purified by flash column chromatography on silica gel eluting with methanol in DCM (0-1-3%). This gave 0.18 g (30%) of white solid: mp 189 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 423; Anal for C ₁₈ H ₁₅ ClN ₂ 0 ₄ S _2. Theoretic (act): C 51.1 (51. 1)%, H 3.6 (3.3)%, N 6.6 (6.4)%.
[1128] Example 90A
[1129] Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate (Note: this experiment describes an attempt to reduce ethyl ester groups to alcohols Example 8 (1.2 g, 3.3 mmol) was dissolved in dry THF (10 mL). Lithium borohydride (0.2 g, 10 mmol) was added in portions at ambient temperature under N ₂ atmosphere. The colored suspension was stirred overnight. Aqueous HC1 (1M, 40 mL) and brine (40 mL) were added before extraction with ethyl acetate. The crude material was obtained by drying (sodium sulfate), and evaporation of the organic phase, which was purified by flash column chromatography on silica gel eluting with methanol (0->2-> 4%) in DCM. This gave 0.36 g (30%) of a yellow solid: mp 187 ° C.; MS (ion spray, [M + H] ⁺ ) m / z 361; Analysis of C _l3 H _l3 ClN ₂ 0 ₄ S _2. Theoretic (actual): C 43.3 (43.1)%, H 3.6 (3.4)%, N 7.8 (7.6)%
[1130] Example 91A
[1131] Methyl {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -5-methyl-1,3-thiazol-4-yl} acetate
[1132] The title compound was prepared from methyl 2- (2-amino-5-methyl-1,3-thiazol-4-yl) acetate and 4-biphenylsulfonyl chloride as described in Synthesis Method B, with a purity> 90. A white solid (22.1 mg) with% was obtained. LCMS (pos) m / z 403.0.
[1133] Example 92A
[1134] Methyl (2-{[(4-chlorophenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate
[1135] The title compound was prepared from methyl 2- (2-amino-5-methyl-1,3-thiazol-4-yl) acetate and 4-chlorobenzenesulfonyl chloride as described in Synthesis Method B, with a purity> 90. A white solid (29.2 mg) with% was obtained. LCMS (pos) m / z 361.2.
[1136] Example 93A
[1137] Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate
[1138] The title compound is prepared from methyl 2- (2-amino-5-methyl-1,3-thiazol-4-yl) acetate and 3-chloro-2-methylbenzenesulfonyl chloride as described in Synthesis Method B. A white solid (23.2 mg) was obtained having a purity> 90%. LCMS (pos) m / z 375.2.
[1139] Example 94A
[1140] Methyl [2-({[4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -5-methyl-1,3-thiazol-4-yl] acetate
[1141] Methyl 2- (2-amino-5-methyl-1,3-thiazol-4-yl) acetate and 4- (3-chloro-2-cyanophenoxy) benzenesulfonyl as described in Synthesis Method B The title compound was prepared from chloride to give a yellow solid (28.3 mg) with a purity> 90%. LCMS (pos) m / z 478.2.
[1142] Example 95A
[1143] Methyl (5-methyl-2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1144] The title compound was prepared from methyl 2- (2-amino-5-methyl-1,3-thiazol-4-yl) acetate and 4-n-propylbenzenesulfonyl chloride as described in Synthesis Method B, and the purity> A white solid (33.1 mg) was obtained having 90%. MS (pos) m / z 416.2.
[1145] Example 96A
[1146] Methyl (5-methyl-2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate
[1147] The title compound is prepared from methyl 2- (2-amino-5-methyl-1,3-thiazol-4-yl) acetate and 2,4,6-trichlorobenzenesulfonyl chloride as described in Synthesis Method B. To give a white solid (60.8 mg) with a purity> 90%: MS (pos) m / z 431. 1; _{HRMS m / z 427.9233 (C l3} H ll Cl 3 N 2 0 4 is the value of a single isotope theoretical mass element for the S ₂ 427.9226).
[1148] Example 97A
[1149] Methyl (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate
[1150] The title compound was prepared from methyl 2- (2-amino-5-methyl-1,3-thiazol-4-yl) acetate and 2,4-dichloro-6-methylbenzenesulfonyl chloride as described in Synthesis Method B. To give a white solid (27.2 mg) with a purity> 80%. MS (pos) m / z 409.0, 411.0.
[1151] Example 98A
[1152] N- (2-methoxyethyl) -2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide
[1153] Example 84A (0.5 g, 1.6 mmol) in DCM (15 mL) was treated by drop with oxalyl chloride (0.3 g, 2.4 mmol). A catalytic amount of DMF was added and the resulting orange mixture was stirred for 2 hours. The solvent was removed under reduced pressure and the raw material was suspended in 4 mL of DCM. The suspension was added dropwise to a solution of DIEA (0.62 g, 4.8 mmol) and 2-methoxyethylamine (0.24 g, 3.2 mmol) and stirred at ambient temperature for 3 hours. The organic phase was washed with 2M aqueous HCl, dried (magnesium sulfate) and evaporated. The crude brown solid was recrystallized from ethyl acetate to give 0.11 g (19%) of the pure title compound: mp 132 ° C .; IR (KBr) υ 3328,1316,1146,1090 ° C. m ⁻¹ ; MS (ion spray, [M + H] ⁺ ) m / z 370; Analysis for _{C l5 H l9 N 3 0 4} S 2 Calcd (found):. C 48.8 (48.8) %, H 5.2 (5.2)%, N 11. 4 (11.3)%.
[1154] Example 99A
[1155] 2- (2-{[(2,5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N methylacetamide
[1156] The title compound was prepared from Example 85A according to the preparation described for Example 98A. Recrystallization from acetone / diethyl ether / petroleum ether gave 0.03 g (8%) of a white solid: mp 183 ° C .; IR (KBr) υ 3326,1300, 1154 cm ⁻¹ ; MS (ion spray, [M + H] ⁺ ) m / z 385; _{Anal for C10} H ₉ Cl ₂ N ₃ 0 ₃ S _3. Theoretic findings: C 31.1 (31.4)%, H 2.4 (2.7)%, N 10.9 (10.5)%.
[1157] Example 100A
[1158] N- (1,3-benzodioxol-5-ylmethyl) -2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide
[1159] According to Method C, then Method E, the title compound was prepared from Example 76A to yield 66 mg (16%) of pure product. MS (ion spray, [M + H] &lt; + &gt;) m / z 482; _{C 23 H l9 N 3 0 5} S 2 · 0.3 DMF analysis of the theoretical value (measured value):. C 57.0 (56.6) % H 4. 2 (4.0)% N 9.2 (8.9)%.
[1160] Example 101A
[1161] N- (2-furylmethyl) -2- {2-[(l-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide
[1162] According to Method C, followed by Method E, the title compound was prepared from Example 76A to yield 98 mg (27%) of a white solid: MS (ion spray, [M + H] + m / z 428; C ₂₀ H ₁₇ Analysis for N ₃ O ₄ S ₂ .0.1 CH ₂ Cl _2. Theoretical value: found C 55.4 (55.3)% H 4. 0 (3.6)% N 9. 6 (9.3)%.
[1163] Example 102A
[1164] 2- (2-{[(2,4-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide
[1165] The title compound was prepared from Example 4A according to Method D.
[1166] Recrystallization from acetone / ether / petroleum ether gave 0.09 g (40%) of a pink solid: mp 150 ° C .; IR (KBr) ν 3304,3087,1325, 1150 ° C. m ⁻¹ ; MS (ion spray, [M + H] ⁺ ) m / z 362; _{Anal for} C ₁₃ H ₁₃ F ₂ N ₃ 0 ₃ S _2. Theoretical values: found C 43.2 (43.1)%, H 3.6 (3.2)%, N 11.6 (11.2)%.
[1167] Example 103A
[1168] N-isopropyl-2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide
[1169] Method C, followed by the titled compound from Example 76A according to the method E, to give the pure product in 122mg (36%): MS (Ion Spray, [M + H] +) m / z 390; C l8 H l9 Analysis for N ₃ 0 ₃ S ₂ .0.2CH ₂ C1 _2. Theoretic (act.): C 53.8 (54.0)% H 4. 8 (4.4)% N 10. 3 (10.1)%.
[1170] Example 104A
[1171] N- [2- (lH-indol-3-yl) ethyl] -2- {2-[(l-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide
[1172] The title compound was prepared from Example 76A according to Method C, followed by Method E to give 134 mg (32%) of pure product: MS (ion spray, [M + H] ⁺ ) m / z 391; Anal for C ₂₅ H ₂₂ N ₄ 0 ₃ S ₂ 0.2 CH ₂ C1 _2. Theoretical value: found C 59.6 (59.7)% H 4. 4 (4.1)% N 11.0 (10.7)%.
[1173] Example 105A
[1174] N- (cyclohexylmethyl) -2- {2-[(phenylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide
[1175] The title compound was prepared from Example 20A according to Method C, followed by Method E, and 134 mg (25%) of pure product was obtained after recrystallization from DCM: MS (ion spray, [M + H] ⁺ ) m / z 394 ; Analysis of C ₁₈ H ₂₃ N ₃ O ₃ S ₂ .0.3 H ₂ 0. Theoretical value: found 54.2 (54.2)% H 6.0 (5.3)% N 10.5 (10.1)%.
[1176] Example 106A
[1177] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide
[1178] The title compound was prepared from Example 8A according to Method D and obtained 0.20 g (61%) of a pink solid: mp 165 ° C .; IR (KBr) υ 3334,3085,1318,1142 cm ^-1 ; MS (ion spray, [M + H] &lt; + &gt;) m / z 360; Anal for C ₁₃ H ₁₄ ClN ₃ O ₃ S _2. Theoretical values: found C 43.4 (43.4)%, H 3. 9 (3.6)%, N 11.7 (11.3)%.
[1179] Example 107A
[1180] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide
[1181] The title compound was prepared from Example 8A according to Method D to give 0.18 g (53%) of a yellow solid: mp 96 ° C .; IR (KBr) υ 3327,3098,1136 cm ^-1 ; MS (ion spray, [M + H] ⁺ ) m / z 374; C ₁₄ H ₁₆ ClN ₃ O ₃ S ₂ .0. Analyzes for 2 H ₂ 0. Theoretic (actual): C 44.5 (44.4)%, H 4.4 (3.9)%, N ll.l (10.7)%.
[1182] Example 108A
[1183] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide
[1184] The title compound was prepared from Example 87A according to Method E and obtained 0.10 g (34%) of a pink solid after recrystallization from ethyl acetate / ether / petroleum ether: mp 202 ° C .; IR (KBr) υ 3313, 3107, 1308, 1133 cm ⁻¹ ; MS (ion spray, [M + H] ⁺ ) m / z 422; Analysis of C ₁₈ H ₁₆ ClN ₃ O ₃ S _2. Theoretical value: found C 51.2 (50.9)%, H 3.8 (3.6)%, N 10.0 (9.5)%.
[1185] Example 109A
[1186] 2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N- (2-furylmethyl) acetamide
[1187] The title compound was prepared from Example 2A according to Method C, followed by Method E, and after recrystallization from DCM, 172 mg (35%) of pure product were obtained: MS (ion spray, [M + H] ⁺ ) m / z 412 ; Analysis for C ₁₆ H ₁₄ ClN ₃ O ₄ S ₂ .0.3 H ₂ O. Theory. Found: C 46.1 (46.1)% H 3. 5 (3.1)% N 10.1 (9.8)%.
[1188] Example 110A
[1189] N-benzhydryl-2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide
[1190] The title compound was prepared from Example 2A according to Method C, followed by Method E, and 157 mg (26%) of pure product was obtained after recrystallization from DCM: MS (ion spray, [M + H] ⁺ ) m / z 498 ; Anal for C ₂₄ H ₂₀ ClN ₃ 0 ₃ S ₂ -0.6 H ₂ O. Theoretical value: found 56.6 (56.5)% H 4.2 (3.6)% N 8.3 (8.0)%.
[1191] Example 111A
[1192] 2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N- (tetrahydro-2-furanylmethyl) acetamide
[1193] According to Method C followed by Method E, the title compound was prepared from Example 2A and 92 mg (18%) of pure product was obtained after recrystallization from DCM: MS (ion spray, [M + H] ⁺ ) m / z 416; Analysis for _{C l6 H l8 ClN 3 0 4} S 2 Calcd (found):. C 46.2 (45.9) % H 4.3 (3.9)% N 10.1 (9.7)%.
[1194] Example 112A
[1195] Ethyl 4-{[2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] amino} -1-piperidinecarboxylate
[1196] According to Method C, then Method E, the title compound was prepared from Example 2A and 281 mg (48%) of pure material was obtained after recrystallization from DCM: MS (ion spray, [M + H] ⁺ ) m / z 487 ; Anal for C ₁₉ H ₂₃ ClN ₄ 0 ₅ S _2. Theoretical value: found C 46.9 (46.8)% H 4.8 (4.6)% N 11.5 (11.2)%.
[1197] Example 113A
[1198] N-benzhydryl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide
[1199] According to Method E, the title compound was prepared from Example 87A and 0.09 g (20%) of a pink solid was obtained after recrystallization from acetone / diethyl ether: mp 200 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 512.
[1200] Example 115A
[1201] 2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide
[1202] According to Method C, then from Example 2A, from Example 2A, the title compound was prepared and 130 mg (26%) of pure product was obtained after recrystallization from ethanol: MS (ion spray, [M + H] ⁺ ) m / z 407; Anal for C ₁₇ H ₁₄ ClN ₃ 0 ₃ S _2. Theoretical value: found 50.0 (49.6)% H 3.5 (3.3)% N 10.3 (10.3)%.
[1203] Example 116A
[1204] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide
[1205] A solution of Example 8A (0.20 g, 0.53 mmol) in concentrated ammonium hydroxide (6 mL) was stirred at rt overnight. The solvent was evaporated to give quantitative yield of the title product: MS (ion spray, [M + H] ⁺ ) m / z 345; Analysis for _{C l4 H l6 N 2 0 5} S 2 Calcd (Found): C 42. 0 (42.5) % H 3.5 (3.3)% N 11.3 (11.4)%.
[1206] Example 117A
[1207] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diethylacetamide
[1208] The title compound was prepared according to Method E. The resulting product mixture was separated on a silica gel column to give the amide (53 mg, 0.13 mmol, 11%) and the decarboxylated product 3-chloro-2-methyl-N- (4-methyl-1,3-thiazole-2 -Yl) benzenesulfonamide (135 mg, 0.44 mmol, 39%) was obtained. Example 117A: MS (ion spray, [M + H] ⁺ ) m / z 401; Anal for C ₁₆ H ₂₀ ClN ₃ 0 ₃ S _2. Theoretical value: found 47.8 (47.7)% H 5.0 (5.4)% N 10 .4 (10.2)%.
[1209] Example 119A
[1210] 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diethylacetamide
[1211] The title compound was prepared by coupling Intermediate 11 and 4-biphenylsulfonyl chloride according to Method B: MS (ion spray, [MH] ⁻ ) m / z 428.3.
[1212] Example 120A
[1213] N, N-diethyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide
[1214] The title compound was prepared by coupling Intermediate 11 and 4-propylbenzenesulfonyl chloride according to Method B: MS (ion spray, [MH] ⁻ ) m / z 393. 4.
[1215] Example 121A
[1216] 2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diethylacetamide
[1217] The title compound was prepared by coupling Intermediate 11 and 2,4-dichloro-6-methylbenzenesulfonyl chloride according to Method B: MS (ion spray, [MH] ⁻ ) m / z 434.3.
[1218] Example 122A
[1219] N, N-diethyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide
[1220] The title compound was prepared by coupling Intermediate 11 and 2,4,6-trichlorobenzenesulfonyl chloride according to Method B: MS (ion spray, [MH] ⁻ ) m / z 454.2.
[1221] Example 123A
[1222] 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diisopropylacetamide
[1223] The title compound was prepared by coupling Intermediate 14 and 4-biphenylsulfonyl chloride according to Method B: MS (ion spray, [M-H]-) m / z 456.4.
[1224] Example 124A
[1225] N, N-diisopropyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide
[1226] The title compound was prepared by coupling Intermediate 14 and 4-propylbenzenesulfonyl chloride according to Method B: MS (ion spray, [MH] ⁻ ) m / z 422.6.
[1227] Example 125A
[1228] 2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diisopropylacetamide
[1229] The title compound was prepared by coupling Intermediate 14 and 2,4-dichloro-6-methylbenzenesulfonyl chloride according to Method B: MS (ion spray, [MH] ⁻ ) m / z 462.2.
[1230] Example 126A
[1231] N, N-diisopropyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide
[1232] The title compound was prepared by coupling Intermediate 14 and 2,4,6-trichlorobenzenesulfonyl chloride according to Method B: MS (ion spray, [MH] ⁻ ) m / z 482.3.
[1233] Example 127A
[1234] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diisopropylacetamide
[1235] The title compound was prepared by coupling Intermediate 14 and 3-chloro 2-methylbenzenesulfonyl chloride according to Method B: MS (ion spray, [MH] ⁻ ) m / z 427.9.
[1236] Example 128A
[1237] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dipropylacetamide
[1238] The title compound was prepared by coupling Intermediate 15 and 3-chloro-2-methylbenzenesulfonyl chloride according to Method B: MS (ion spray, [MH] ⁻ ) m / z 428.3.
[1239] Example 129A
[1240] N-benzyl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide
[1241] Using N-methylbenzylamine, the title compound was prepared in 51% yield from Example 87A according to Method E: MS (electronic spray, [M + H] ⁺ ) m / z 450.2.
[1242] Example 130A
[1243] N-benzyl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide
[1244] According to Method F, the title compound was prepared from Example 87A.
[1245] Pink solid (346 mg, 75%) was obtained after completion of reaction and purification by flash chromatography: MS (ion spray, [M + H] ⁺ ) m / z 464.0; Anal for C _2l H ₂₂ ClN ₃ 0 ₃ S _2. Theoretical value: found 54.4 (54.2)%, H 4.8 (4.7)%, N 9.1 (9.1)%.
[1246] Example 131A
[1247] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dimethylacetamide
[1248] According to Method D, the title compound was prepared from Example 8A.
[1249] After completion of reaction and purification by flash column chromatography, a pink solid (75 mg, 38%) was obtained: mp 84-84 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 374. 0; C _l4 H _l6 ClN ₃ 0 ₃ S ₂ Analysis of the theoretical value (measured value):. C 45.0 (44.8) %, H 4.3 (4.5)%, N 11.2 (11. 0)%.
[1250] Example 132A
[1251] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-cyclohexyl-N-methylacetamide
[1252] The title compound was prepared in 52% yield from Example 87A according to Method E using N-methylcyclohexylamine: MS (Electronic Spray, [M + H] ⁺ ) m / z 442.2.
[1253] Example 132B
[1254] 3-chloro-N- {4- [2- (3,4-dihydro-2 (1H) -isoquinolinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2 Methylbenzenesulfonamide
[1255] Using 3,4-dihydro-2 (1H) -isoquinoline, the title compound was prepared in 29% yield from Example 87A according to Method E: MS (electronic spray, [M + H] ⁺ ) m / z 462.0.
[1256] Example 133A
[1257] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N-phenylacetamide
[1258] Using N-methylaniline, the title compound was prepared in 57% yield from Example 87A according to Method E: MS (electronic spray, [M + H] ⁺ ) m / z 436.2.
[1259] Example 134A
[1260] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-isopropyl-N-methylacetamide
[1261] The title compound was prepared in 66% yield from Example 87A according to Method E using N-methylisopropylamine: MS (Electronic Spray, [M + H] ⁺ ) m / z 402.2.
[1262] Example 135A
[1263] 2- {2-1 ([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-isopropyl-N-methylacetamide
[1264] The title compound was prepared by coupling Intermediate 9 and 4-biphenylsulfonyl chloride according to Method B to afford 108 mg (47%) of product: MS (electronpray, [MH] ⁻ ) m / z 428.4.
[1265] Example 136A
[1266] N-ethyl-N-methyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide
[1267] The title compound was prepared by coupling Intermediate 8 and 2,4,6-trichlorobenzenesulfonyl chloride according to Method B to afford 180 mg (75%) of product: MS (Electrospray, [MH] ⁻ ) m / z 440.2.
[1268] Example 137A
[1269] 2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N-methylacetamide
[1270] The title compound was prepared by coupling Intermediate 8 and 2,4-dichloro-6-methylbenzenesulfonyl chloride according to Method B to give 27 mg (12%) of the product: MS (Electrospray, [MH] ⁻ m / z 420.2.
[1271] Example 138A
[1272] N-ethyl-N-methyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1, 3-thiazol-4-yl) acetamide
[1273] The title compound was prepared by coupling Intermediate 8 and 4-n-propylbenzenesulfonyl chloride according to Method B to give 115 mg (56%) of the product: MS (electronic spray, [MH] ⁻ ) m / z 380.3.
[1274] Example 139A
[1275] 2- {2-[(l, 1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-ethyl-N-methylacetamide
[1276] The title compound was prepared by coupling Intermediate 8 and 4-biphenylsulfonyl chloride according to Method B to give 143 mg (64%) of product: MS (electronic spray, [MH] ⁻ ) m / z 414.3.
[1277] Example 140A
[1278] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N-methylacetamide
[1279] The title compound was prepared in 63% yield from Example 87 according to Method E using N-methylethylamine: MS (electronic spray, [M + H] ⁺ ) m / z 388.2.
[1280] Example 141A
[1281] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N [(lS) -1 -phenylethyllacet amides
[1282] Using (1S) -l-phenylethylamine, the title compound was prepared in 45% yield from Example 87A according to Method E: MS (electrospray, [M + H] ⁺ ) m / z 464.2.
[1283] Example 142A
[1284] 3-chloro-2-methyl-N- {4- [2-oxo-2- (l-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1285] According to Method G, the title compound was prepared from Example 8A.
[1286] After purification by reaction finishing and flash column chromatography, a pale brown foam was obtained. This material was recrystallized from methanol to give 139 mg (66%) of amber crystals: mp 107 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 400.0; C ₁₆ H ₁₈ ClN ₃ O ₃ S ₂ .1 MeOH.0. Analyzes for 25 H ₂ O. Theoretic (actual): C 46.8 (46.8)%, H 5.2 (5.2)%, N 9.6 (9.5)%.
[1287] Example 143A
[1288] 3-chloro-2-methyl-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1289] Example 8A (200 mg, 0.53 mmol) was heated in a Heck vial at 100 ° C. for 3 days in piperidine (2 mL). The reaction mixture was cooled to room temperature and then the brown crystals formed were collected in a filter: MS (ion spray, [M + H] ⁺ ) m / z 414.2.
[1290] Example 144A
[1291] N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide
[1292] The title compound was prepared by coupling Intermediate 13 and 4 biphenylsulfonyl chloride according to Method B to afford 122 mg (51%) of product: MS (electronic spray, [MH] ⁻ ) m / z 440.4.
[1293] Example 145A
[1294] N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide
[1295] The title compound was prepared by coupling Intermediate 13 and 4-n-propylbenzenesulfonyl chloride according to Method B to give 146 mg (66%) of the product: MS (electronic spray, [MH] ⁻ ) m / z 406.4.
[1296] Example 146A
[1297] 2,4-dichloro-6-methyl-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1298] The title compound was prepared by coupling Intermediate 13 and 2,4-dichloro-6-methylbenzenesulfonyl chloride according to Method B to give 168 mg (69%) of the product: MS (electronic spray, [MH] ⁻ m / z 446.3.
[1299] Example 147A
[1300] 2,4,6-trichloro-N- {4- [2-oxo-2- (l-piperidinyl) ethyll-1,3-thiazol-2-yl} benzenesulfonamide
[1301] The title compound was prepared by coupling Intermediate 13 and 2,4,6-trichlorobenzenesulfonyl chloride according to Method B to give 156 mg (62%) of product: MS (electronic spray, [MH] ⁻ ) m / z 466 3.
[1302] Example 148A
[1303] 3-chloro-2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1304] According to Method F, the title compound was prepared from Example 87A.
[1305] Pink foam was obtained after completion of reaction and purification by flash chromatography. This material was recrystallized from methanol to give pink crystals (0.83 g, 69%): mp 208-209 ° C.; MS (ion spray, [M + H] ⁺ ) m / z 416.0; Anal for C ₁₆ H ₁₈ ClN ₃ 0 ₄ S _2. Theoretical value: found C 46.2 (46.0)%, H 4.4 (4.6)%, N 10.1 (10.0)%.
[1306] Example 149A
[1307] 2,4,6-trichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1308] The title compound was prepared by coupling Intermediate 10 and 2,4,6-trichlorobenzenesulfonyl chloride according to the preparation of Example 152A to give 162 mg (64%) of the product: MS (electronic spray, [MH] ^-) m / z 470.1.
[1309] Example 150A
[1310] 2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1311] The title compound was prepared by coupling Intermediate 10 and 2,4-dichloro-6-methylbenzenesulfonyl chloride according to the preparation of Example 152A, to give 111 mg (46%) of the product: MS (electronic spray, [ MH] ^- ) m / z 448.1.
[1312] Example 151A
[1313] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl] -4-sulfonamide
[1314] Intermediate 10 (123 mg, 0.54 mmol) and DMAP (66 mg, 0.54 mmol) were mixed with TEA (0.15 mL, 1.08 mmol) and DMF (1 mL). 4-biphenylsulfonyl chloride (137 mg, 0.54 mmol) was added. The mixture was left at rt overnight, after which gasoline ether (35 mL) was added. The separated oil was purified by chromatography on silica gel (15 mL) eluting with DCM and 5% MeOH / DCM to give 22 mg (9%) of the title compound: MS (electronic spray, [MH] ⁻ ) m / z 442.2.
[1315] Example 152A
[1316] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide
[1317] Intermediate 10 (123 mg, 0.54 mmol) and DMAP (66 mg, 0.54 mmol) were mixed with pyridine (1 mL) and cooled on ice. 4-n-propylbenzenesulfonyl chloride (118 mg, 0.54 mmol) was added. The mixture was kept at 4 ° C. overnight. The reaction mixture was then heated to 50 ° C. over 1.5 hours, cooled and left at room temperature for 4.5 hours. The solvent was evaporated and the residue was purified by flash chromatography on silica gel with 0-5% MeOH / DCM as eluent to afford 122 mg (55%) of the title compound: MS (electronic spray, [MH] ^{-) m / z 408: 3} .
[1318] Example 153A
[1319] 2,4-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1320] Intermediate 10 (0.227 g, 1.00 mmol) and DMAP (0.122 g, 1.00 mmol) were dissolved in DMF (2.0 mL) and diisopropylethylamine (0.258 g, 2.00 mmol) and DCM (1.5 mL). 2,4-Dichlorobenzenesulfonyl chloride (0.245 g, 1.00 mmol) in DCM (1.0 mL) was added to the mixture and the reaction stirred overnight. The reaction mixture was filtered through a Hydromatrix column treated with aqueous hydrogen chloride (10 mL, 1 M) and eluted with DCM. The washed solution was concentrated and purified by silica chromatography using DCM / methanol (95: 5) to give 177 mg (41%) of the title compound with HPLC purity> 90%: MS (ion spray, [MH] ^-) m / z 434.2; 436.2,438.2.
[1321] Example 154A
[1322] 4-chloro-2,6-dimethyl-N- {4-12- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1323] The title compound was prepared using 4-chloro-2, 6 dimethyl-benzenesulfonyl chloride according to Example 153A, to give 43 mg (10%) of product with HPLC purity> 90%: MS (ion spray, [ M + H] ⁺ ) m / z 430.0.
[1324] Example 155A
[1325] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-phenoxybenzenesulfonamide
[1326] Using the 4-phenoxybenzenesulfonyl chloride according to Example 153A, the title compound was prepared to yield 117 mg (25%) of product with 90% HPLC purity: MS (ion spray, [MH] ⁻ ) m / z 458.3.
[1327] Example 156A
[1328] 2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) benzenesulfonamide
[1329] According to Example 153A, the title compound was prepared using 2-methyl-4- (trifluoromethoxy) benzenesulfonyl chloride to give 129 mg (29%) of product with HPLC purity> 90%: MS ( Ion spray, [M ⁻ H] ⁻ ) m / z 464.2.
[1330] Example 157A
[1331] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2,4-bis (trifluoromethyl) benzenesulfonamide
[1332] According to Example 153A, the title compound was prepared using 2,4 bis (trifluoromethyl) benzenesulfonyl chloride and 98 mg (19%) of product with HPLC purity> 90% were obtained: MS (ion spray , [M ⁻ H] ⁻ ) m / z 502.2.
[1333] Example 158A
[1334] 4-bromo-2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1335] According to Example 153A, the title compound was prepared using 4-bromo-2 methyl-benzenesulfonyl chloride, and 73 mg (16%) of product with HPLC purity> 90% were obtained: MS (ion spray, [ M + H] ⁺ ) m / z 460.0,462.0.
[1336] Example 158B
[1337] 4- (2-furyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1338] The title compound was prepared from furan-2-boronic acid (17 mg) as described in Synthesis Method L to give a beige solid (11.6 mg) having a purity> 80%. MS (pos) m / z 434. 1.
[1339] Example 158C
[1340] 3'-fluoro-6'-methoxy-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1, 1 ' -Biphenyl] -4-sulfonamide
[1341] The title compound was prepared from 5-fluoro-2-methoxyphenylboronic acid (25 mg) as described in Synthesis Method L to give a white solid (33.3 mg) with a purity> 90%: MS (pos) m / z 492.0; HRMS m / z 491.0987 (Theoretical value of single isotope mass for C ₂₂ H ₂₂ FN ₃ 0 ₅ S ₂ is 491.0985).
[1342] Example 158D
[1343] 4- (5-methyl-2-thienyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1344] The title compound was prepared from 5-methylthiophene-2-boronic acid (21 mg) as described in Synthesis Method L to give a white solid (7.1 mg) having a purity> 90%. MS (pos) m / z 464.1.
[1345] Example 158E
[1346] 3'-acetyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl] -4- Sulfonamide
[1347] The title compound was prepared from 3-acetylphenylboronic acid (25 mg) as described in Synthesis Method L to give a white solid (33.2 mg) having a purity> 90%. MS (pos) m / z 486.1.
[1348] Example 158F
[1349] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4 '-(trifluoromethoxy) [l, l'-ratio Phenyl] -4-sulfonamide
[1350] The title compound was prepared from 4- (trifluoromethoxy) benzeneboronic acid (31 mg) as described in Synthesis Method L to give a white solid (30.4 mg) with a purity> 90%. MS (pos) m / z 528.1.
[1351] Example 158G
[1352] 3 ', 4'-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide
[1353] The title compound was prepared from 3,4-dichlorophenylboronic acid (29 mg) as described in Synthesis Method L to give a white solid (27.3 mg) with a purity> 90%: MS (pos) m / z 512.0, 514.0; HRMS m / z 511.0196 (Theoretical value of single isotope mass for C _2l H ₁₉ Cl ₂ N ₃ 0 ₄ S ₂ is 511. 0194).
[1354] Example 158H
[1355] 4- (1,3-benzodioxol-5-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzene Sulfonamide
[1356] The title compound was prepared from 3,4-methylenedioxyphenylboronic acid (25 mg) as described in Synthesis Method L to give a brown solid (5.2 mg) having a purity> 80%. MS (pos) m / z 488.1.
[1357] Example 158I
[1358] 4- (5-chloro-2-thienyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1359] The title compound was prepared from 5-chlorothiophene-2-boronic acid (24 mg) as described in Synthesis Method L to give a white solid (5.1 mg) having a purity> 90%. MS (pos) m / z 484.0,486.0.
[1360] Example 158J
[1361] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (4-pyridinyl) benzenesulfonamide
[1362] The title compound was prepared from pyridine-4-boronic acid (18 mg) as described in Synthesis Method L, but with more palladium (II) acetate (4 mg) at a temperature of 100 ° C., a white having a purity> 90%. A solid (4.0 mg) was obtained. MS (pos) m / z 445.0.
[1363] Example 158K
[1364] N- {4 '-[({4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [1,1'- Biphenyl] -3-yl} acetamide
[1365] The title compound was prepared from 3-acetamidobenzeneboronic acid (27 mg) as described in Synthesis Method L to give a white solid (3.0 mg) having a purity> 90%. MS (pos) m / z 501.2.
[1366] Example 158L
[1367] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (3-thienyl) benzenesulfonamide
[1368] The title compound was prepared from thiophen-3-boronic acid (19 mg) as described in Synthesis Method L to give a beige solid (22.4 mg) with a purity> 90%: MS (pos) m / z 450.0; _{HRMS m / z 449.0543 (C l9} H l9 N 3 0 4 S ₃ 449.0538 the value of the theoretical mass for single isotope).
[1369] Example 158M
[1370] N- {4-12- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (2-thienyl) benzenesulfonamide
[1371] The title compound was prepared from thiophene-2-boronic acid (19 mg) as described in Synthesis Method L to give a beige solid (6.1 mg) having a purity> 90%. MS (pos) m / z 450.1.
[1372] Example 158N
[1373] 4 '-[({4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [1,1'-biphenyl] 4-carboxylic acid
[1374] The title compound was prepared from 4-carboxyphenylboronic acid (25 mg) as described in Synthesis Method L to give a white solid (12.4 mg) having a purity> 80%. MS (pos) m / z 488.1.
[1375] Example 158O
[1376] 4 '-(methylsulfanyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl ] -4-sulfonamide
[1377] The title compound was prepared from 4- (methylthio) phenylboronic acid (25 mg) as described in Synthesis Method L to give a beige solid (30.0 mg) with a purity> 90%. MS (pos) m / z 490.1.
[1378] Example 158P
[1379] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3 ', 5'-bis (trifluoromethyl) [l, l'-biphenyl] -4-sulfonamide
[1380] The title compound was prepared from 3,5-bis (trifluoromethyl) phenylboronic acid (39 mg) as described in Synthesis Method L to give a beige solid (39.6 mg) with a purity> 90%. MS (pos) m / z 580.1.
[1381] Example 158Q
[1382] 4'-chloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4- Sulfonamide
[1383] The title compound was prepared from 4-chlorophenylboronic acid (23 mg) as described in Synthesis Method L to give a beige solid (31. 1 mg) having a purity> 90%. MS (pos) m / z 478.1.
[1384] Example 158R
[1385] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3'-nitro [l, l'-biphenyl] -4- Sulfonamide
[1386] The title compound was prepared from 3-nitrophenylboronic acid (25 mg) as described in Synthesis Method L to give a white solid (34.8 mg) with a purity> 90%: MS (pos) m / z 489.1; HRMS m / z 488.0827 (Theoretical value of monoisotopic mass for C ₂₁ H ₂₀ N ₄ O ₆ S ₂ is 488.0824).
[1387] Example 158S
[1388] 4- (1-benzofuran-2-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1389] The title compound was prepared from benzo [B] furan-2-boronic acid (24 mg) as described in Synthesis Method L to give a yellow solid (4.7 mg) with a purity> 80%. MS (pos) m / z 484.0.
[1390] Example 158T
[1391] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (1-pyrrolidinyl) benzenesulfonamide
[1392] The title compound was prepared from pyrrolidine (71 mg) as described in Synthesis Method N to give a solid (0.6 mg) with a purity> 90%. MS (pos) m / z 437.0.
[1393] Example 158U
[1394] 4- (4-methyl-1-piperidinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1395] The title compound was prepared from 4-methylpiperidine (99 mg) as described in Synthesis Method N to give a solid (2.1 mg) having a purity> 80%. MS (pos) m / z 465.2.
[1396] Example 158V
[1397] 4-anilino-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1398] The title compound was prepared from aniline (93 mg) as described in Synthesis Method N to give a solid (4.6 mg) with a purity> 90%. MS (pos) m / z 459.2.
[1399] Example 158 W
[1400] 4- (benzylamino) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1401] The title compound was prepared from benzylamine (16 mg) as described in Synthesis Method M to give a solid (2.0 mg) having a purity> 80%. MS (pos) m / z 473.2.
[1402] Example 158X
[1403] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(2-thienylmethyl) amino] benzenesulfonamide
[1404] The title compound was prepared from thiophene-2-methylamine (113 mg) as described in Synthesis Method N to give a solid (0.7 mg) having a purity> 90%. MS (pos) m / z 479.1.
[1405] Example 158Y
[1406] 4- (4-morpholinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1407] The title compound was prepared from morpholine (13 mg) as described in Synthesis Method M to give a solid (8.3 mg) with a purity> 90%. MS (pos) m / z 453. 1.
[1408] Example 158Z
[1409] 4- (4-methyl-1-piperazinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1410] The title compound was prepared from N-methylpiperazine (15 mg) as described in Synthesis Method M to give a solid (3.9 mg) with a purity> 80%. MS (pos) m / z 466.2.
[1411] Example 158ZA
[1412] N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(3-pyridinylmethyl) amino] benzenesulfonamide
[1413] The title compound was prepared from 3- (aminomethyl) pyridine (108 mg) as described in Synthesis Method N to give a solid (0.9 mg) with a purity> 70%. MS (pos) m / z 474.1.
[1414] Example 159A
[1415] 2,4-dichloro-6-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1416] The title compound was prepared essentially from Intermediate 16 and 2,4-dichloro-6-methylbenzenesulfonyl chloride according to Method B. Ivory crystals were obtained after recrystallization from methanol in this procedure (117 mg, 60%): mp 186-187 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 464.0.
[1417] Example 160A
[1418] N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl] -4-sulphone amides
[1419] The title compound was prepared essentially from Intermediate 16 and 4-biphenylsulfonyl chloride according to Method B. This procedure yielded a greyish white solid material after column chromatography and softening with methanol (75 mg, 39%): mp 204-206 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 458.0; Anal. For C ₂₂ H ₂₃ N ₃ 0 ₄ S ₂ · 1 H ₂ 0. Theoretical (actual): C 55.6 (55. 2)%, H 5.3 (5.3)%, N 8.8 (8.9)%.
[1420] Example 161A
[1421] 2,4,6-trichloro-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1422] The title compound was prepared essentially from Intermediate 16 and 2,4,6-trichlorobenzenesulfonyl chloride according to Method B. In this procedure ivory crystals (151 mg, 74%) were obtained after recrystallization from methanol: mp 216-217 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 486.0; _{Anal for} C ₁₆ H ₁₆ Cl ₃ N ₃ 0 ₄ S ₂ .1 CH ₃ 0H. Theoretical values: C 39.5 (39.2)%, H 4.0 (3.9)%, N 8.1 (8.1)%.
[1423] Example 162A
[1424] 3-chloro-2-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1425] The title compound was prepared essentially from Intermediate 16 and 3-chloro-2-methylbenzenesulfonyl chloride according to Method B. In this procedure ivory crystals (105 mg, 58%) were obtained after recrystallization from methanol: mp 194-195 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 430.2; Analysis for _{C l7 H 20 ClN 3 0 4} S 2 · 0.5 H 2 0 Calcd (Found): C 46. 5 (46.9) %, H 4.8 (4.6)%, N 9.6 (9.6)%.
[1426] Example 163A
[1427] 3-chloro-N- (4- {2-[(2R, 6S) -2,6-dimethylmorpholinyl] -2-oxoethyl} -1,3-thiazol-2-yl) -2-methyl Benzenesulfonamide
[1428] The title compound was prepared in 19% yield from Example 87A and cis- (2R, 6S) 2,6-dimethylmorpholine following the preparation of Example 171A: MS (Electronic Spray, [MH] ⁻ ) m / z 442.3 .
[1429] Example 164A
[1430] 3-chloro-2-methyl-N- (4- {2-[(lS, 4S) -2-oxa-5-azabicyclo] [2.2.1] hept-5-yl] -2-oxoethyl}- 1,3-thiazol-2-yl) benzenesulfonamide
[1431] Example 87A (40 mg, 0.115 mmol), (1S, 4S)-(+)-2-aza-5-oxabicyclo [2.2.1] heptane hydrochloride (16 mg, 0.12 mmol) and DMAP (15 mg, 0.12 mmol ) Was dissolved in DMF (0.3 mL). EDCI (23 mg, 0.12 mmol) was added followed by diisopropylethylamine (41 I1L, 0.24 mmol). The solution was left overnight, evaporated in vacuo and the residue was purified by flash-chromatography on silica gel with 2% and 5% methanol / DCM as eluent. Yield 36 mg, 73%: MS (electronic spray, [MH] ⁻ ) m / z 426.3.
[1432] Example 165A
[1433] 3-chloro-2-methyl-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl) benzenesulfonamide
[1434] According to Method G, the title compound was prepared from Example 8A using thiomorpholine. After reaction finishing and purification by flash chromatography, a pale pink solid (150 mg, 66%) was obtained: mp 103-106 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 432.2; Analysis of C ₁₆ H ₁₈ ClN ₃ O ₃ S _3. Theoretic (actual): C 44.5 (44.4)%, H 4.2 (4.4)%, N 9.7 (9.5)%.
[1435] Example 166A
[1436] N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyll-1,3-thiazol-2-yl} [l, l'-biphenyl] -4-sulfonamide
[1437] According to Method B, the title compound was prepared by coupling Intermediate 12 and 4-biphenylsulfonyl chloride to give 104 mg (42%) of product: MS (electronic spray, [MH] ⁻ ) m / z 458. 3.
[1438] Example 167A
[1439] N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide
[1440] According to Method B, the title compound was prepared by coupling Intermediate 12 and 4-n-propylbenzenesulfonyl chloride to give 171 mg (74%) of product: MS (electronic spray, MH) ^- ) m / z 424.2.
[1441] Example 168A
[1442] 2,4-dichloro-6-methyl-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1443] According to Method B, the title compound was prepared by coupling Intermediate 12 and 2,4 dichloro-6-methylbenzenesulfonyl chloride to give 145 mg (57%) of the product: MS (electronic spray, [MH] ^-) m / z 464.3.
[1444] Example 169A
[1445] 2,4,6-trichloro-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1446] According to Method B, the title compound was prepared by coupling Intermediate 12 and 2,4,6 trichlorobenzenesulfonyl chloride to afford 114 mg (43%) of the product: MS (electronic spray, [MH] ⁻ ) m / z 484.1.
[1447] Example 170A
[1448] N- {4- [2- (1,1-dioxido-4-thiomorpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide
[1449] Example 167A (43 mg, 0.1 mmol) was mixed with methanol (1 mL) and cooled on ice. Oxone (potassium peroxymonosulfate, 74 mg, 0.12 mmol) dissolved in water (81 mL) was added slowly. The mixture was stirred at rt overnight. Methanol was evaporated, water was added and the mixture was neutralized with sodium bicarbonate and extracted with DCM. The product was purified by flash chromatography using 5% methanol / DCM as eluent. Yield 16 mg, 35%: ¹ HNMR (DMSO) δ 7.65 (d, 2H), 7.35 (d, 2H), 6.5 (s, 1H), 3.85 (m, 4H), 3. 75 (s, 2H), 3.25 (m, 2H), 3.1 (m, 2H), 2.6 (t, 2H), 1.6 (m, 2H), 0.9 (t, 3H). MS-ES (neg) m / z 456.2:
[1450] Example 171A
[1451] Tert-butyl-4-[(2-{((3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] -1-piperazinecarboxylate
[1452] Example 87A (278 mg, 0.8 mmol), t-butyl 1-piperazinecarboxylate (126 mg, 1.0 mmol) and DMAP (25 mg, 0.2 mmol) were stirred in DMF (3 mL). After 3 days, DMF was removed in a rotary evaporator and the residue was purified by flash chromatography on silica gel with 5% methanol / DCM as eluent to afford 111 mg (27%) of the title compound: ¹ H NMR (CDC1 ₃ ) δ 7.98 (d, 1H), 7.53 (d, 1H), 7.22 (t, 1H), 6.35 (bs, 1H), 3.81 (s, 2H), 3.3-3.65 (m, 9H), 2.60 (s, 3 H), 1.44 (s, 9 H). MS-ES (neg) m / z 513. 2.
[1453] Example 171B
[1454] N- {4- [2- (4-acetyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3-chloro-2-methylbenzenesulfonamide
[1455] This compound was prepared using N-acetylpiperazine following the procedure for synthesis of Example 171A. In this way 133 mg (49%) of the title compound were obtained after purification: 1 H NMR (DMSO) δ 7.90 (d, 1H), 7.67 (d, 1H), 7.39 (t, 1H), 6.52 (s, 1H), 3.68 (s, 2H), 3.4-3.5 (8H), 2.64 (s, 3H), 2.02 (s, 3H). MS-ES neg m / z 455.4.
[1456] Example 172A
[1457] 3-chloro-2-methyl-N- {4-12- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluoro acetate
[1458] To an ice-cooled suspension of Example 8A (2.43 g, 6.44 mmol) in DCM (60 mL) was added HOBT (0.98 g, 6.44 mmol), EDCI (1.23 g, 6.44 mmol) and Et3N (1.30 g, 12.89 mmol). Added. The mixture was stirred for 10 minutes when 1-methylpiperazine (704 mg, 7.03 mmol) was added. The reaction was run overnight at room temperature and then extracted with 1 M HCl containing some water. The product solidified into the organic phase and it was separated. Solvent was evaporated and the residue was dissolved in TFA. The solution was placed on top of the column and the crude material was purified by reverse phase flash chromatography on LiChroprep RP-18. The product was eluted gradient with (acetonitrile / 0.4% concentrated HC1 in H ₂ O). The pure portion was pooled and the solvent volume was reduced by about 70%. A precipitate formed which was centrifuged and the clear yellow solvent was removed. The solid was dried under vacuum at 60 ° C. to give a white solid (1.30 g, 2.79 mmol, 48%): Mp 245 ° C. dec .; MS (ion spray, [M + H] ⁺ ) m / z 428; _{C l7 H 2l ClN 4 0 3} S 2 · 1 HCl · 0.4 H ₂ 0 analysis of the theoretical value (measured value):. C 43.2 (43.2) % H 4.9 (4.9)% N 11.8 (11.9)%.
[1459] Example 173A
[1460] 3-chloro-2-methyl-N- {4- [2-oxo-2- (l-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluoroacetate
[1461] The title compound was prepared from Example 171A as described for the BOC-deprotection procedure in the preparation of Example 177A: MS-ES (neg) m / z 415.2.
[1462] Example 174A
[1463] 2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) Benzenesulfonamide
[1464] Starting from ethyl [2-({[2-methyl-4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3 thiazol-4-yl] acetate (2.80 g, 6.30 mmol) The title compound was synthesized in two steps as described for Example 175A, yielding 116 mg (48% yield) of product with 95% HPLC purity: ¹ H NMR (CDC1 ₃ ) δ 8.03 (d, 1 H) , 7.05 (m, 2H), 6.28 (s, 1H), 3.70 (s, 2H), 3.55 (m, 2H), 3.46 (m, 2H), 2.50 (s, 3H), 2.38 (m, 4H), 2.25 (s, 3H).
[1465] Example 175A
[1466] 2,4-dichloro-6-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1467] Example 30A (1.91 g, 4.67 mmol) was added to a solution of potassium hydroxide (5 g, 89 mmol) in water (25 mL) and ethanol (25 mL). The reaction was stirred overnight, diluted with water and washed with toluene. The water phase was adjusted to pH 1 with aqueous hydrogen chloride (37%) and the solution extracted with ethyl acetate. The combined ethyl acetate layers were dried (magnesium sulfate) and concentrated to 1.7 g (95% yield) of (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazole -4-yl) acetic acid was obtained. ( ¹ H NMR (DMSO-d ₆ ) δ 7.61 (d, 1 H), 7.50 (d, 1 H), 6.62 (s, 1 H), 3.56 (s, 2 H), 2.68 (s, 3 H) MS (ion spray, [M + H] &lt; + &gt;) m / z 381. 0). Acid (0.2 g, 0.525 mmol) was coupled with 1-methyl-piperazine as in Method F to give 110 mg (45% yield) of the title compound with 95% HPLC purity: ¹ H NMR ((: DC1 ₃ ) δ 7.29 (d, 1 H), 7.15 (d, 1 H), 6.35 (s, 1 H), 3.55 (s, 2 H), 3.60 (m, 2 H), 3. 49 (m, 2H), 2.74 (s, 3H), 2.41 (m, 4H), 2.28 (s, 3H) .MS (ion spray, [M + H] ⁺ ) m / z 463.0.
[1468] Example 176A
[1469] 2,4-dichloro-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1470] The title compound was synthesized in two steps as described for Example 175A starting from Example 32A (1.60 g, 4.05 mmol) to give 10 mg (4% yield) of product with 95% HPLC purity: ¹ H NMR (CDC1 ₃ ) δ 8.08 (d, 1 H), 7.42 (d, 1 H), 7.33 (dd, 1 H), 6.39 (s, 1 H), 3.62 (m, 2 H), 3.52 ( m, 2H), 3.46 (s, 2H), 2.43 (m, 4H), 2.55 (s, 3H). MS (ion spray, [M + H] ⁺ ) m / z 449.0,450.0,451.0.
[1471] Example 177A
[1472] 3-chloro-N- (4- {2-[(2R) -2,4-dimethylpiperazinyl] -2-oxoethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulphone amides
[1473] Example 87A (347, 1.0 mmol) and Intermediate 7 (240 mg, 1.2 mmol) were coupled using Method F to give 260 mg (49%) of t-butyl (3R) -4-[(2-{[ (3-Chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] -3-methyl-1-piperazinecarboxylate was obtained ( ¹ H NMR (CDC1 ₃ ) δ 7.97 (d, 1H), 7.50 (d, 1H), 7. 19 (t, 1H), 6.31 (bs, 1H), 4.68, 4.28 (m, 1H), 2.62 (s, 3H), 1.44 (s , 9H), 1.19,1.13 (d, 3H), MS-ES (neg) m / z 527.3). This intermediate was treated with TFA / DCM / water (2 mL, 10: 9: 1 v / v / v) and stirred for 1 hour. Evaporation of the volatiles gave 231 mg (87%) of deprotection product as the TFA salt (MS-ES (pos) m / z 429.2). This product (225 mg, 0.4 mmol) was mixed with TEA (110 μL, 0.79 mmol) and 1,2-dichloroethane (2.0 mL). 37% formalin (65 gel, 0.86 mmol) was added followed by sodium triacetoxyborohydride (200 mg, 0.95 mmol). The mixture was stirred overnight, 5% aqueous sodium bicarbonate was added and the product extracted with ethyl acetate. The organic phase was dried and evaporated. The residue was passed through a LiChroprep RP-18 column (Merck) and eluted with 40% acetonitrile, 1% acetic acid / water. This procedure yielded 85 mg (50%) of the title compound: MS-ES (neg) m / z 441.4.
[1474] Example 178A
[1475] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methoxy-N-methylacetamide
[1476] Example 87A (346 mg, 1.0 mmol) was coupled to O, N-dimethylhydroxylamine hydrochloride (117 mg, 1.2 mmol) using Method F. After completion of the reaction, 382 mg of a tan brown solid was obtained which was purified by flash column chromatography eluting with DCM / methanol (20: 1 v / v). The pure portion was pooled and after evaporation of the solvent, triturated with DCM / diethylether (1: 1 v / v) to afford 300 mg (77%) of a pale pink solid: mp 168-169 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 390; C ₁₄ H ₁₆ ClN ₃ O ₄ S ₂ .0. Analyzes for 5 H ₂ 0. Theoretic (act): C 42.2 (41.9)%, H 4.3 (4.2)%, N 10.5 (10.3)%.
[1477] Example 179A
[1478] 3-chloro-2-methyl-N- [4- (2-oxopentyl) -1,3-thiazol-2-yl] benzenesulfonamide
[1479] Under nitrogen (g) atmosphere, Example 178A (200 mg, 0.51 mmol) was dissolved in THF (4 mL) and cooled to 0 ° C. n-propylmagnesium chloride (0.52 mL, 2M in diethyl ether) was added dropwise through a septum with a syringe. The resulting bright green solution was warmed to room temperature and quenched with aqueous HCl (1 M, 5 mL). Extract with DCM (3 × 5 mL) and dry organic phase (sodium sulfate) and evaporate in vacuo to afford crude yellow oil. Purification by flash chromatography on silica gel eluting with DCM / methanol (20: 1 v / v) gave 10 mg of a white solid: MS (ion spray, [M + H] ⁺ ) m / z 373.0; HRMS Calcd (found) m / z 372.0361 (372. 0369 ) for _{C l5 H l7 ClN 2 0 3} S 2.
[1480] Example 180A
[1481] 4-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] benzenesulfonamide
[1482] Starting with Example 2A, the title compound was prepared following the preparation of Example 181A. This gave a crude product which was purified by flash column chromatography on silica gel eluting with 20% acetone in DCM to give 635 mg (36%) pure material: MS (ion spray, [M + H] ⁺ ) m / z 318; Anal for C ₁₁ H ₁₁ ClN ₂ 0 ₃ S _2. Theoretical value: found 41.4 (41.3)% H 3.5 (3.5)% N 8.8 (8.6)%.
[1483] Example 181A
[1484] 3-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide
[1485] To a solution of Example 8A (5.00 g, 13.34 mmol) in THF (200 mL) was added lithium aluminum hydroxide (1.06 g, 28.02 mmol) in small portions. During the addition, the temperature was kept below 0 ° C. and the mixture was stirred at 0 ° C. for 45 minutes and treated with water (1 mL), concentrated HC1 (1 mL) and water (1 mL). Sodium sulfate was added and the solid was filtered off. The solvent was evaporated and the crude product was purified by flash column chromatography on silica gel eluting with 20% acetone in DCM to afford the title compound (2.41 g, 54%): MS (ion spray, [M + H] ⁺ ) m / z 332; Analysis for _{C l2 H l3 ClN 2 0 3} S 2 Calcd (found):. C 43.3 (46.5) % H 3.9 (4.0)% N 8.4 (8.3)%.
[1486] Example 181B
[1487] 3-chloro-N- [4- (3-hydroxypropyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide
[1488] To a solution of Example 231B (1.91 g, 4.91 mmol) in DME (10 mL) was added lithium borohydride (180 mg, 7.86 mmol). The mixture was refluxed for 3 hours and acetic acid (2 mL) was added at room temperature. At the end of gas evolution, 2-ethanolamine (1 mL) was added and the mixture was refluxed for an additional 40 minutes. Solvent was evaporated and the residue was extracted with 2 M HCl and THF. The organic phase was separated and the solvent was evaporated. The residue was crystallized from ethanol to give 1.56 g (91%) of the title compound: ¹ H NMR (DMSO) δ 1.66 (qn, 2H), 2.46 (t, 2H), 2.64 (s, 3H), 3.68 (t , 2H), 6.41 (s, 1H), 7.37 (t, 1H), 7.66 (d, 1H), 7.89 (d, 1H); MS (ion spray, [M + H] ⁺ ) m / z 346.
[1489] Example 182A
[1490] 3-chloro-N- [4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide
[1491] To a stirred solution of Example 181A (426 mg, 1.28 mmol) in tetrahydrofuran (10 mL) at room temperature was added sodium hydroxide (95% dry, 80 mg, 3.23 mmol). After stirring for 15 minutes, the mixture was treated with ethyl iodide (400 mg, 2.56 mmol). The reaction mixture was stirred for 2 h at 55 ° C. and then quenched with aqueous HCl (1 M, 1 mL) and water was added. The product was extracted with DCM and dried (sodium sulfate). The solvent was evaporated to give a residue which was purified by flash chromatography on silica gel eluting with 10% acetone in DCM to give an oil (0.25 g, 54%) which solidified as it was: MS (ion spray, [M + H] ⁺ ) m / z 360; C _l4 H _l7 ClN ₂ 0 ₃ S ₂ analysis of the theoretical value (measured value):. C 46.6 (46.5) % H 4.7 (4.6)% N 7.8 (7.8)%.
[1492] Example 183A
[1493] 3-chloro-N- [4- (2-isopropoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide
[1494] To a stirred solution of Example 181A (359 mg, 1.08 mmol) in THF (10 mL) at room temperature was added sodium hydroxide (95% dry, 129 mg, 5.39 mmol). After stirring for 15 minutes, the mixture was treated with 2-iodopropane (917 mg, 5.39 mmol). After 2-day at 50 ° C., additional sodium hydroxide (26 mg, 1.08 mmol) and 2-iodopropane (366 mg, 2.16 mmol) were added. After stirring for 1 hour the reaction mixture was acidified with 2M HC1 and water was added. The product was extracted with DCM and dried (sodium sulfate). The solvent was evaporated to give a residue, which was purified by flash chromatography on silica gel eluting with 4% acetone in DCM to give (15 mg, 4%) of oil which solidified as it was. : MS (ion spray, [M + H] ⁺ ) m / z 374.
[1495] Example 184A
[1496] N- {4- [2- (benzyloxy) ethyl] -1,3-thiazol-2-yl} -3-chloro-2-methylbenzenesulfonamide
[1497] Sodium hydroxide (95% dry, 76 mg, 3.00 mmol) was added to a stirred solution of Example 181A (400 mg, 1. 20 mmol) in THF (10 mL) at room temperature. After stirring for 15 minutes, the mixture was treated with benzyl bromide (226 mg, 1.32 mmol).
[1498] After 2 hours at 50 ° C., additional sodium hydroxide (60 mg, 2.40 mmol) and benzyl bromide (142 mg, 1.20 mmol) were added in two equal portions for 2 hours. The reaction was quenched by adding 1M HC1 (3 mL) at room temperature. The mixture was extracted with DCM and dried (sodium sulfate). The solvent was evaporated to give a residue, which was purified by flash chromatography on silica gel eluting with 5% acetone in DCM to give (105 mg, 0.25 mmol, 21%) which solidified as it was: MS (ion spray, [M ^{+ H] +) m / z} 322. C l9 H 19 ClN 2 0 3 S 2 · 0. Analysis of 5 CH ₂ C1 _2. Theoretic (actual): C 50.3 (50.7)% H 4.3 (4.1)% N 6.0 (5.9)%.
[1499] Example 185A
[1500] 3-chloro-N- [4- (2-methoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide
[1501] The title compound was prepared from Example 181A following the preparation of Example 182A using methyl iodide. After 1.5 h at 40 ° C. the reaction mixture was quenched with 2M HC1 (1 mL) and water was added. The mixture was extracted with DCM and dried (sodium sulfate). The solvent was evaporated to give a residue which was purified by flash chromatography on silica gel eluting with 5% acetone in DCM to give a colorless oil (0.25 g, 60%) which solidified as is: MS (ion spray, [ ^{m + H] +) m /} z 346. C l3 H l5 ClN 2 0 3 S ₂ analysis of the theoretical value (measured value):. C 45.0 (44.8) % H 4.4 (4.4)% N8. 1 (7.9)%.
[1502] Example 186A
[1503] 3-chloro-N- {4- [2- (2-fluoroethoxy) ethyll-1,3-thiazol-2-yl} -2-methylbenzenesulfonamide
[1504] The title compound was prepared from Example 181A following the preparation of Example 182A using 1-fluoro-2-iodoethane (6 eq). After 5 hours at reflux the reaction mixture was quenched with 2M HCl and water was added. The mixture was extracted with DCM and dried (sodium sulfate). The solvent was evaporated to give a residue, which was purified by flash chromatography on a silica gel gradient eluting with 0-20% acetone in DCM to give a colorless oil (28 mg, 6%). MS (ion spray, [M + H] ⁺ ) m / z 378.
[1505] Example 187A
[1506] 3-chloro-2-methyl-N- {4- [2- (2,2,2-trifluoroethoxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1507] To a stirred solution of 2,2,2-trifluoroethanol (1.00 g, 10.00 mmol) in THF (15 mL) at 0 ° C. was added sodium hydroxide (95% dry, 253 mg, 10.00 mmol). After stirring at room temperature for 15 minutes, the temperature was lowered to -80 ° C using an ethanol-dry ice bath. Trifluoromethanesulfonyl chloride (1.69 g, 10.00 mmol) dissolved in THF (5 mL) was then added in portions, and the mixture was then left to reach room temperature overnight. The reaction mixture was centrifuged and the white precipitate separated. The solvent was diluted to 25 mL with THF (estimated concentration: 0.4 M). 2,2,2-trifluoro prepared in a mixture of Example 181A (500 mg, 1.5 mmol) and sodium hydroxide (95% dry, 94 mg, 3.73 mmol) in THF (10 mL) at 0 ° C. under nitrogen atmosphere Ethyl trifluoromethanesulfonate solution (7.5 mL, 0.4 M) was added. After stirring for 1.5 h at 0 ° C., an additional amount of sodium hydroxide (95% dry, 76 mg, 3.00 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate solution (7.5 mL) were added. After 1 h ice was poured into the mixture at 0 ° C., neutralized with 2.0 M HG1 and extracted with DCM. The organic solvent was evaporated to give a residue, which was purified by flash chromatography on silica gel gradient eluted with 2-5% acetone in DCM. This as a white solid 174mg (28%): MS analysis of the (Ion ^{Spray, [M + H] +)} m / z 414. C l4 H l4 ClF 3 N 2 0 3 S 2 Calcd (found). : C 40.5 (40.5)% H 3.4 (3.4)% N 6.7 (6.7)%.
[1508] Example 188A
[1509] 3-chloro-2-methyl-N- {4- [2- (2-pyridinylsulfanyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1510] To a stirred solution of bromide example 213A (240 mg, 0.61 mmol) and 2-mercaptopyridine (68 mg, 0.61 mmol) in tetrahydrofuran (10 mL) at 0 ° C., sodium hydroxide (95% dry, 31 mg, 1.21). mmol) was added. After stirring at 0 ° C. for 30 minutes, the product formed slowly. After 30 minutes of raising the temperature to 40 ° C., the reaction was neutralized by addition of aqueous HC1 (2 M) and the mixture was extracted with DCM. The organic phase was dried (sodium sulfate) and the solvent was evaporated. The crude material was purified by flash chromatography on silica gel gradient eluted with 2-5% acetone in DCM to give a solid (130 mg, 50%). MS (ion spray, [M + H] ⁺ ) m / z 425; Analysis for _{C l7 H l6 ClN 3 0 2} S 3 Calcd (found):. C 47.9 (47.9) % H 3.8 (3.9)% N 9.9 (9.9)%.
[1511] Example 189A
[1512] 3-chloro-2-methyl-N- {4-12- (3-pyridinyloxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1513] To a stirred solution of bromide example 213A (240 mg, 0.61 mmol) and 3-hydroxypyridine (63 mg, 0.67 mmol) in tetrahydrofuran (10 mL) at 0 ° C. sodium hydroxide (95% dry, 32 mg, 1.27 mmol) ) Was added. After 2 h at reflux, the reaction was neutralized by the addition of 2 M HC1 and the product mixture was extracted with DCM. The organic phase was dried (sodium sulfate) and the solvent was evaporated. The crude material was purified by flash chromatography on silica gel gradient eluted with 2-5% acetone in DCM to give the title compound as a solid (18 mg, 7%) and 3-chloro-2- as a solid (33 mg, 17%). Methyl-N- (4-vinyl-1,3-thiazol-2-yl) benzenesulfonamide was obtained. Example 189A: MS (ion spray, [M + H] ⁺ ) m / z 410.
[1514] Example 189B
[1515] Methyl 2- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethoxy] benzoate
[1516] Intermediate 23 (124 mg, 0.445 mmol) and DMAP (54 mg, 0.44 mmol) were dissolved in DCM (2 mL). TEA (0.12 mL, 0.89 mmol) was added followed by 3-chloro-2-methylbenzenesulfonyl chloride (105 mg, 0.468 mmol). The solution was kept at room temperature overnight and then left at 4 ° C. for 3 days. Chromatography on silica gel with heavy and 35% ethyl acetate / toluene gave the title product (91 mg, 44% yield): MS-ES (neg) m / z 465.5; ¹ H NMR (CDC1 ₃ ) δ 7.99 (m, 2H), 7.4 7.55 (m, 2H), 7.16 (m, 1H), 7.03 (t, 1H), 6.87 (d, 1H), 6.11 (s, 1H) , 4.18 (t, 2H), 3.95 (s, 3H), 3.01 (t, 2H), 2.80 (s, 3H).
[1517] Example 190A
[1518] 3-chloro-N- [5-[(dimethylamino) methyll-4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide
[1519] A solution of Example 182A (360 mg, 1 mmol), dimethylamine hydrochloride (164 mg, 2 mmol), 37% formaldehyde (0,5 mL) in acetic acid (5 mL) was heated at 100 ° C. for 5.5 h. The solvent was evaporated. The residue was dissolved in water (5 mL).
[1520] The pH of the water solution was adjusted to 9 with 2 N NaOH. The precipitate was filtered off, washed with water and dried to give the product as a white powder (115. 4 mg, 28% yield): mp 152-153 ° C .; MS m / e, 420,418 (M ⁺ )
[1521] Example 191A
[1522] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl methanesulfonate
[1523] Example 181A (1.0 g, 3.0 mmol) was suspended in DCM (15 mL) and Et3N (0.9 g, 8.4 mmol) was added dropwise with stirring at 0 ° C. Methane sulfonyl chloride (0.5 g, 4.2 mmol) was added and the colored suspension was warmed to room temperature and stirred for 4 hours. Washed with aqueous HC1 (1 M, 2 × 40 mL), dried (sodium sulfate) and the organic phase was evaporated to afford crude material. Purification by preparative straight phase HPLC gave 0.7 g (54%) of a grayish white solid: MS (ion spray, [M + H] ⁺ ) m / z 411; Analysis for _{C l3 H l5 ClN 2 0 5} S 3 Calcd (found):. C 38.0 (37.9) %, H 3.7 (4.0)%, N 6.8 (6.6)%
[1524] Example 191B
[1525] 3- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) propylmethanesulfonate
[1526] The title compound was prepared essentially according to the synthesis described for Example 191A, starting with Example 181B (1.51 g, 4.36 mmol). After the reaction finishing process, the crude material was purified by flash chromatography on silica gel eluting with 5% acetone in DCM to give 1.00 g (54%) of oil: ¹ H NMR (CDC1 ₃ ) δ 2.63 (s, 3H), 2.77 (s, 3H); 2.87 (s, 3H), 3. 02 t, 2H), 3.44 (t, 2H), 6.34 (s, 1H), 7.24 (t, 1H), 7.55 (dd, 1H), 8.00 (dd, 1H); MS (ion spray, [M + H] ⁺ ) m / z 423.
[1527] Example 192A
[1528] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl acetate
[1529] The title compound was prepared by coupling Example 181A and acetyl chloride according to Method J to give 79 mg (70%) white foam after purification: HRMS theory for C ₁₄ H ₁₅ ClN ₂ O ₄ S ₂ (found) m / z 374.0162 (374.0144).
[1530] Example 192B
[1531] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl propionate
[1532] The title compound was prepared by coupling Example 181A and propionyl chloride according to Method J, and obtained 104 mg (89%) of a white solid after purification: mp 122 ° C .; HRMS theoretical (calculated) for C ₁₅ H ₁₇ ClN ₂ 0 ₄ S ₂ m / z 388.0318 (388.0307).
[1533] Example 193A
[1534] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-methylpropanoate
[1535] The title compound was prepared and purified by coupling Example 181A and isobutyryl chloride according to Method J to give 58 mg (48%) of a white solid: mp 118 ° C .; HRMS Calcd (found) m / z 402.0475 (402.0473) for _{C l6 H 19 ClN 2 0 4} S 2.
[1536] Example 194A
[1537] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-furoate
[1538] The title compound was prepared by coupling Example 181A and 2-furoyl chloride according to Method J to obtain 96 mg (75%) of a white solid after purification: HRMS for C ₁₇ H _l5 ClN ₂ 0 ₅ S ₂ Theoretical (act) m / z 426.0111 (426.0112).
[1539] Example 195A
[1540] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl benzoate
[1541] By coupling the embodiment 181A and benzoyl chloride according to method J to give the titled compound after purification as a white foam of _{104mg (80%): C l9} H l7 ClN 2 0 4 HRMS Calcd for S ₂ (found m / z 436.0318 (436.0314).
[1542] Example 196A
[1543] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 4-morpholinecarboxylate
[1544] 56 mg (42%) of a white solid were obtained after purification and purification using morpholine as amine starting from Example 181A according to Method K: mp 161 ° C .; HRMS theoretical (calculated) for C ₁₇ ClN ₃ O ₅ S ₂ m / z 445.0533 (445.0525).
[1545] Example 197A
[1546] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl diethylcarbamate
[1547] Starting from Example 181A according to Method K and preparing the title compound using N, N-diethylamine as the amine, after purification, 72 mg (56%) of a white solid were obtained: ¹ H NMR (CDC1 ₃ ) δ 1.07-1.10 (m, 6H), 2.68 (s, 3H), 2.99 (t, 2H), 3.21-3.27 (m, 4H), 4.33 (t, 2H), 6.15 (s, 1H), 7.22 (t, 1H), 7.53 (d, 1H), 8.02 (d, 1H), 11.17 (br s, NH).
[1548] Example 198A
[1549] 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl ethylcarbamate
[1550] Starting from the embodiment 181A according to the method and K to give the titled compound was obtained as a N- ethylamine as the amine, after purification of a white solid 78mg (64%): for _{C 15 H l8 ClN 3 0 4} S 2 HRMS theoretical (found) m / z 403.0427 (403.0413).
[1551] Example 199A
[1552] N- [4- (2-azidoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide
[1553] The crude material was extracted with ethyl acetate. The organic phase was dried (sodium sulfate) and the solvent was evaporated. The crude product was purified by flash column chromatography on silica gel eluting with 2-5% acetone in DCM to afford the title product (633 mg, 1.77 mmol, 70%): MS (ion spray, [M + H] ⁺ ). m / z 357.
[1554] Example 200A
[1555] N- [4- (2-aminoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide
[1556] Example 191A (l.OOg, 2.43 mmol) was stirred for 1 h at 25 ° C. in 25% ammonium hydroxide (40 mL). About 10 mL of solvent was evaporated and the solid was filtered off to give 0.69 g (85%) of the pure title compound: ¹ H NMR (DMSO) δ 2.63 (m, 5H), 2. 99 (t, 2H), 6.21 (s, 1 H), 7.24 (t, 1 H), 7.49 (d, 1 H), 7.85 (d, 1 H); MS (ion spray, [M + H] ⁺ ) m / z 331.
[1557] Example 200B
[1558] 3-chloro-2-methyl-N- {4- [2- (methylamino) ethyll-1,3-thiazol-2-yl} benzenesulfonamide
[1559] Example 191A (1. SOg, 3.66 mmol) was stirred in 40% aqueous methylamine (12 mL) at 80 ° C. for 30 minutes. Most solvents were evaporated, water was added and the product was extracted with DCM (150 mL) to afford 1.27 g (volume) of the title compound: ¹ H NMR (DMSO) δ 2.57 (s, 3H), 2.63 (s, 3H), 2.68 (t, 2H), 3.09 (t, 2H), 6.24 (s, 1H), 7.25 (t, 1H), 7.50 (d, 1H), 7.85 (d, 1H); MS (ion spray, [M + H] ⁺ ) m / z 345.
[1560] Example 201A
[1561] 4-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride
[1562] To an ice-cooled solution of Example 180A (1.24 g, 3. 90 mmol) in pyridine (15 mL) 4-nitrobenzenesulfonyl chloride (1.30 g, 5.85 mmo) was added. The mixture was stirred for 2.5 h at 0 ° C. and then poured into a mixture of ice (50 g) and concentrated HC1 (40 g). The resulting precipitate was filtered and the solid was washed with water to yield 1.57 g (80%) of intermediate sulfonate 2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazole-4- I) ethyl 4-nitrobenzenesulfonate was obtained. A solution of this sulfonate (600 mg, 1.19 mmol) and diethylamine (218 mg, 2.98 mmol) in DMF (10 mL) was stirred at 50 ° C. for 3 hours. The solvent was evaporated and the residue was purified by flash column chromatography on silica gel eluting with (DCM: Acetone: HCOOH; 7: 2: 1). The product was purified again by flash column chromatography on RP silica gel gradient eluted with (1% concentrated HC1 in CH ₃ CN / H ₂ O) to give a white solid (40 mg, 8%): MS (ion spray, [ M + H] +) m / z 300; Analytical. Found C ₁₅ H ₂₀ CIN ₃ 0 ₂ S ₂ .1 HCl: C 43.9 (43.8)% H 5.1 (4.8)% N 10.2 (10.0)%.
[1563] Example 202A
[1564] 3-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide hydrochloride
[1565] Following the synthesis described for example 204A, the title compound was prepared and purified using mesylate Example 191A (350 mg, 0.85 mmol), diethylamine (311 mg, 4.26 mmol) and ethanol (5 mL) White solid (150 mg, 0.35 mmol, 41%) was obtained: MS (ion spray, [M + H] ⁺ ) m / z 387; C ₁₆ H ₂₂ CIN ₃ 0 ₂ S ₂ .1 HC1 .0. Analyzes for 3 H ₂ 0. Theoretic (actual): C 44.6 (44.6)% H 5.5 (5.3)% N 9.8 (9.8)%.
[1566] Example 202B
[1567] 3-chloro-N- {4- [2- (lH-imidazol-1-yl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide dihydrate
[1568] To a stirred solution of Example 191A (250 mg, 0.61 mmol) and amidazole (46 mg, 0.67 mmol) in THF (10 mL) at room temperature, NaH (95% dry, 32 mg, 1.28 mmol) was added. When addition amidazole (41 mg, 0.61 mmol) and NaH (95% dry, 15 mg, 0.61 mmol) were added, the mixture was stirred at 40 ° C. for 2 hours. The reaction was allowed to proceed for 1.5 hours and then neutralized by addition of aqueous HC1 (2M). The solvent was evaporated and the resulting crude material was dissolved in TFA and purified by reverse phase flash chromatography on LiChroprep RP-18. The product was gradient eluted with (CH ₃ CN / 0.4% concentrated HC1 in H ₂ O) to give (80 mg, 0.21 mmol, 34%): MS (ion spray, [M + H] ⁺ ) m / z 382. C ₁₅ H _l5 CIN ₄ 0 ₂ S ₂ Analysis of 2 H ₂ 0. Theoretical value (found): C 43.0 (42.9)% H 4.6 (4.3)% N 13.4 (13.7)%.
[1569] Example 203A
[1570] 3-chloro-2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide dihydrochloride
[1571] Using the mesylate Example 191A (300 mg, 0.73 mmol), 1-methylpiperazine (183 mg, 1.82 mmol) and ethanol (5 mL), the title compound was prepared and purified according to the synthesis described for Example 204A. After this a white solid (168 mg, 0.34 mmol, 47%) was obtained: MS (ion spray, [M + H] ⁺ ) m / z 414; _{C l7 H 23 ClN 4 0 2} S 2 · 2 HC1 analysis of the 1.5 H ₂ 0 Calcd (found):. C 39.6 (39.6) % H 5.5 (5.3)% N 10.9 (10.9)%.
[1572] Example 204A
[1573] 3-chloro-2-methyl-N- {4- [2- (4-morpholinyl) ethyll-1,3-thiazol-2-yl} benzenesulfonamide hydrochloride
[1574] To a stirred solution of Example 213A (300 mg, 0.76 mmol) in ethanol (5 mL) was added morpholine (165 mg, 1. 89 mmol). The mixture was refluxed for 1.5 h and the solvent was evaporated. The crude material was purified by reverse phase flash chromatography on LiChroprep RP-18. The product was gradient eluted with (acetonitrile in water / 0.1% concentrated HC1) to give a white solid (177 mg, 53%): Mp 197-198 ° C .; MS (ion spray, [M + H] ⁺ ) m / z 401; Analysis for C ₁₆ H ₂₀ CIN ₃ 0 ₃ S ₂ · 1 HC1. Theoretical value (found): C 43.8 (43.5)% H 4.8 (4.9)% N 9.6 (9.5)%.
[1575] Example 204B
[1576] 3-chloro-2-methyl-N- [4- (4-morpholinylmethyl) -1,3-thiazol-2-yl] benzenesulfonamide hydrochloride
[1577] A mixture of intermediate 19 (0.50 g, 2.70 mmol) and morpholine (1.65 g, 18.92 mmol) was stirred overnight at room temperature. The solvent was evaporated and the solid residue was purified by reverse phase flash chromatography on LiChroprep RP 18. The product was eluted with (1% CH ₃ CN /0.5% concentrated HC1 in H ₂ O) to afford 4- (4-morpholinylmethyl) -1,3-thiazol-2-amine dihydrochloride and mor An about 1: 1 mixture of foline (1.33 g) was obtained. The material was sulfonylated with 3-chloro-2-methylbenzenesulfonyl chloride according to the preparation as described for example 205A to give 17 mg (6%) of solids: ¹ H NMR (DMSO) δ 2.65 (s , 3H), 3.08 (br m, 4H), 3.78 (br m, 4H), 4.13 (br s, 2H), 7.07 (s, 1H), 7.40 (t, 1H), 7.68 (d, 1H), 7.91 (d, 1H); MS (ion spray, [M + H] &lt; + &gt;) m / z 387.
[1578] Example 205A
[1579] 2,4,6-trichloro-N- {4- [2- (4-morpholinyl) ethyll-1,3-thiazol-2-yl} benzenesulfonamide hydrochloride
[1580] To a mixture of intermediate 17 (50 mg, 0.23 mmol) and sodium bicarbonate (39 mg, 0.47 mmol) in acetone (5 mL) at room temperature, 2,4,6-trichlorobenzenesulfonyl chloride (79 mg, 0.28 mmol) was added It was. The reaction mixture was refluxed and the solvent evaporated for 45 minutes. The crude material was purified by reverse phase flash chromatography on LiChroprep RP-18. The product was gradient eluted with (acetonitrile / 0.4% concentrated HC1 in H ₂ O) to give a white solid (59 mg, 0.12 mmol, 52%): MS (ion spray, [M + H] ⁺ ) m / z 372; C ₁₅ H ₁₆ C ₁₃ N ₃ O ₃ S _{2 .1 HCl.0} . Analysis of 7 H ₂ 0. Theory (actual): C 35.6 (35.7)% H 3.7 (3.5)% N 8.3 (7.6)%.
[1581] Example 206A
[1582] 2,4-dichloro-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride
[1583] Description for Example 205A using Intermediate 17 (100 mg, 0.47 mmol), sodium bicarbonate (79 mg, 0.94 mmol), 2,4-dichlorobenzenesulfonyl chloride (150 mg, 0.61 mmol) and acetone (10 mL) The title compound was prepared and purified following purification to give a white solid (88 mg, 0.19 mmol, 41%): MS (ion spray, [M + H] ⁺ ) m / z 421; C _l5 H _l7 Cl ₂ N ₃ 0 ₃ S ₂ · 1 HC1 · 1.1 H ₂ O Analyzes. Theoretical value: found: C 37. 6 (37. 7)% H 4. 3 (4.5)% N 8. 8 (8.7)%.
[1584] Example 206B
[1585] 2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride
[1586] Intermediate 17 (100 mg, 0.47 mmol), sodium bicarbonate (79 mg, 0.94 mmol), 2,4, -dichloro-6-methylbenzenesulfonylchloride (158 mg, 0.61 mmol), according to the synthesis described for Example 205A And acetone (10 mL) to prepare the title compound, which after purification gave a solid (60 mg, 0.13 mmol, 27%): MS (ion spray, [M + H] ⁺ ) m / z 435. C _{l6 H l9 Cl 2 N 3 0 3} S 2 · 1 HC1 analysis of the theoretical value (measured value):. C 40.6 (40.4) % H 4.3 (4.3)% N 8.9 (8.6)%.
[1587] Example 206C
[1588] N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl-}-4-propylbenzenesulfonamide hydrochloride
[1589] Intermediate 17 (100 mg, 0.47 mmol), sodium bicarbonate (79 mg, 0.94 mmol), 4-n-propylbenzenesulfonyl chloride (133 mg, 0.61 mmol) and acetone (10 mL) according to the synthesis described for Example 205A The title compound was prepared using to give a solid (17 mg, 0.04 mmol, 8%): MS (ion spray, [M + H] +) m / z 495.
[1590] Example 207A
[1591] 3-chloro-N- {4- [2- (ethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide
[1592] A mixture of ethylamine (2M in THF 3.2 mL) and Example 191A (0.100 g, 0.244 mmol) in THF (2 mL) was heated in a sealed glass tube at 60 ° C. for 48 hours. The solvent was removed and the crude material was purified by silica gel chromatography eluting with 10% methanol in DCM. The product was isolated as a white solid (0.044 g, 50% yield): ¹ H NMR (CD ₃ 0D) δ 7.75 (dd, 1 H), 7.52 (dd, 1 H), 7.23 (dt, 1 H), 6.37 (s, 1H), 3.20 (t, 2H), 3.04 (q, 2H), 2.81 (t, 2H), 2.71 (d, 3H), 1.29 (t, 3H); LCMS (pos) m / z 360.0
[1593] Example 208A
[1594] 3-chloro-N- (4- {2-[(2-hydroxyethyl) amino] ethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulfonamide
[1595] Example 191A (0.100 g, 0.244 mmol) was heated with 2-aminoethanol (0.150 g, 2.44 mmol) in THF (1.5 mL) at 60 ° C. for 5 hours. The solvent was removed and the crude yellow oil was dissolved in methanol and eluted through Hydromatrix Chemelute CE1003 filled with saturated aqueous sodium hydrogen carbonate (1 mL) using DCM / methanol (25 mL 1.5 / 1 v / v). The material was purified by silica gel chromatography eluting with 10% methanol in DCM. The title compound was isolated as pale yellow oil (36 mg, 39% yield): ¹ H NMR (CD ₃ 0D) δ 7.95 (d, 1 H), 7.5 (d, 1 H), 7.25 (t, 1 H), 6.35 (s, 1H), 3.80 (dd, 2H), 3.21 (t, 2H), 3.08 (m, 2H), 2.82 (t, 2H), 2.72 (s, 3H). LCMS (pos) m / z 375.9
[1596] Example 208B
[1597] 3-chloro-N- (4- {3-[(2-hydroxyethyl) amino] propyl} -1,3-thiazol-2-yl) -2-methylbenzenesulfonamide hydrochloride hydrate
[1598] 2-ethanolamine (1.43 g, 23.37 mmol) was added to Example 191B (993 mg, 2.34 mmol) and the mixture was stirred at 60 ° C. for 2 hours. Solid formed. Water was added at room temperature and the mixture was centrifuged. The solvent was decanted, filtered and evaporated. The filtrate residue was flash chromatographed on RP silica gel eluting with 20% acetonitrile in H ₂ 0/1% concentrated HCl to give 184 mg (18%) of the title product: MS (ion spray, [M + H ] ⁺ ) m / z 389. Anal. for C ₁₅ H ₂₀ ClN ₃ 0 ₃ S ₂ · 1 HC1 .1.8 H ₂ O. Theoretical value: found: C 39. 3 (39. 3)% H 5.4 (5.5) % N 9.2 (9.3)%.
[1599] Example 209A
[1600] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N-ethylacetamide
[1601] Example 207A (40 mg, 0.11 mmol) was dissolved in pyridine (0.3 mL). Acetyl chloride (12 mg, 0.13 mmol) was added and the reaction stirred at ambient temperature for 1 hour. DCM (25 mL) was added and the organic phase was extracted with aqueous HC1 (25 mL, 2 M) and dried over sodium sulphate. Removal of solvent in vacuo gave the title product (46 mg, 100% yield) as a white solid: LCMS (pos) m / z 402.2.
[1602] Example 210A
[1603] 3-chloro-2-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1604] The title compound was prepared from Intermediate 6 (27 mg, 0.118 mmol) and 3-chloro-2-methylbenzenesulfonyl chloride (45 mg, 0.20 mmol) according to Method A. The crude reaction mixture was dissolved in DCM (25 mL) and washed with aqueous HC1 (2 M, 2 × 25 mL). The organic phase was dried (sodium sulfate), filtered and the solvent removed in vacuo to yield 50 mg of crude material. Purification on RP gel chromatography (gradient of acetonitrile in water, 25-50% with 0.1% TFA) gave a pale yellow solid (29 mg, 46%): LCMS (pos) m / z 416.1.
[1605] Example 210B
[1606] 3-chloro-N- {4- [2- (2-hydroxy-3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide
[1607] To a slurry of Example 208A (0.759 g, 2.02 mmol) in ethyl acetate (6 mL) and saturated sodium carbonate (6 mL) at 0 ° C., 2,2-dichloroacetic acid chloride was added in portions neat. (15 × 40 μL, 3 eq.). The mixture was stirred at rt for 1.5 h. The reaction mixture was then extracted with ethyl acetate (3 x 40 mL), washed with brine (40 mL) and dried over magnesium sulfate. The solvent was evaporated and 1.10 g of crude N-acetylated product was isolated as a yellow oil (70% pure by HPLC). Crude 2, 2-dichloro-N- [2-{[(3-chloro-2 methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N- (2-hydroxy Ethyl) acetamide (1.00 g, 2.05 mmol) was dissolved in THF (27 mL) and water (27 mL). The solution was cooled to 0 ° C. and the pH adjusted to 14-15 with aqueous KOH (50%). After 20 hours, the reaction mixture was neutralized with aqueous HC1 (1 M, 12 mL). The reaction mixture was extracted with ethyl acetate (3 x 25 mL) and the combined organic phases were dried over magnesium sulfate. The solvent was removed to give the title compound as a (gradient of 2-4% methanol in DCM) as a white solid (20mg) Purification by silica gel chromatography: HRMS Calcd (found) for _{C l6 H 18 ClN 3 0 5} S 2 m / z 431.0376 (431.0380).
[1608] Example 210C
[1609] 2,4-dichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyll-1,3-thiazol-2-yl} benzenesulfonamide
[1610] Intermediate 6 (264 mg, 1.0 mmol) and DMAP (122 mg, 1.0 mmol) were mixed with DCM (2.5 mL) and Et3N (0.28 mL, 2.0 mmol). 2,4-dichlorobenzenesulfonyl chloride (270 mg, 1.1 mmol) was added. The resulting solution was left overnight at room temperature. An additional 98 mg (0.4 mmol) of sulfonyl chloride was added and the solution left again overnight. The solvent was evaporated and aqueous sodium carbonate (1 M, 20 mL) was added and the solution extracted with diethyl ether (20 + 10 mL). The aqueous phase was neutralized with HCl and the precipitate was filtered off. The product was purified by flash chromatography on silica gel using 5% methanol / DCM as eluent. Yield 265 mg, 61% ^l H NMR (DMSO) δ 8.01 (d, 1H), 7.8 (d, 1H), 7.59 (dd, 1H), 6.57 (s, 1H), 3.95 (s, 2H), 3.76 ( t, 2H), 3.53 (t, 2H), 3.26 (t, 2H), 2.68 (t, 2H); MS-ES (neg) m / z 434.3.
[1611] Example 210D
[1612] 2,4-dichloro-6-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1613] The title compound was prepared according to the method described for Example 210C. Yield 142 mg, 32%: ¹ H NMR (DMSO) δ 7.59 (d, 1H), 7.48 (d, 1H), 6.54 (s, 1H), 3.95 (s, 2H), 3.76 (t, 2H), 3.52 ( t, 2H), 3.25 (t, 2H), 2.67 (s, 3H), 2.67 (2H); MS-ES (neg) m / z 448.3.
[1614] Example 210E
[1615] 2,4,6-trichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1616] The title compound was prepared according to the method described for Example 210C. Yield 228 mg, 48%: ¹ H NMR (DMSO) δ 7.80 (s, 2H), 6.60 (s, 1H), 3.96 (s, 2H), 3.76 (t, 2H), 3: 53 (t, 2H), 3.26 (t, 2 H); MS-ES (neg) m / z 470.3.
[1617] Example 210F
[1618] 4,5-dichloro-N- [4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-thiophenesulfonamide
[1619] The title compound was prepared according to the method described for Example 210C. Yield 136 mg, 77%: ¹ H NMR (DMSO) δ 7.61 (s, 1H), 6.67 (s, 1H), 3.94 (s, 2H), 3.77 (t, 2H), 3.54 (t, 2H), 3.27 ( t, 2H), 2.70 (t, 2H); MS-ES (pos) m / z 442.
[1620] Example 210G
[1621] N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -4-phenoxybenzenesulfonamide
[1622] The title compound was prepared according to the method described for Example 210C. Yield 142 mg, 77%: ¹ H NMR (DMSO) δ 7.76 (d, 2H), 7.44 (t, 2H), 7.22 (t, 1H), 7.0-7.15 (m, 4H), 6.51 (s, 1H), 3.95 (s, 2H), 3.76 (t, 2H), 3.51 (t, 2H), 3.25 (t, 2H), 2.65 (t, 2H); MS-ES (pos) m / z 460.
[1623] Example 210H
[1624] 3-fluoro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1625] The title compound was prepared according to the method described for Example 210C. Yield 128 mg, 83%: ¹ H NMR (DMSO) δ 7.39-7.67 (m, 4H), 6. 55 (s, 1H), 3.94 (s, 2H), 3.75 (t, 2H), 3.52 (t, 2H ), 3.25 (t, 2 H), 2.66 (t, 2 H); MS-EI m / z 385.
[1626] Example 210I
[1627] N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -5- (2-pyridinyl) -2- thiophensulfonamide
[1628] The title compound was prepared according to the method described for Example 210C. Yield 74 mg, 41%: ¹ H NMR (DMSO) δ 8.54 (d, 1H), 7.98 (d, 1H), 7.87 (m, 1H), 7.76 (d, 1H), 7.54 (d, 1H), 7.35 ( m, 1H), 6.61 (s, 1H), 3.95 (s, 2H), 3.75 (t, 2H), 3.52 (t, 2H), 3.25 (t, 2H), 2.68 (t, 2H); MS-ES (pos) m / z 451.
[1629] Example 210J
[1630] N- {2-chloro-4-[({4-12- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} amino) sulfonyl] phenyl} acetamide
[1631] The title compound was prepared according to the method described for Example 210C. Yield 62 mg, 34%: ¹ H NMR (DMSO) δ 12.85 (bs, 1H), 9.70 (s, 1H, 7.98 (d, 1H), 7.77 (s, 1H), 7.70 (d, 1H), 6.54 (s , 1H), 3.95 (s, 2H), 3.75 (t, 2H), 3.51 (t, 2H), 3.25 (t, 2H), 2.66 (t, 2H), 2.12 (s, 3H); MS-ES ( pos) m / z 459.
[1632] Example 210K
[1633] 3-chloro-2-methyl-N- {4-[(3-oxo-4-morpholinyl) methyll-1,3-thiazol-2-yl} benzenesulfonamide
[1634] A mixture of intermediate 21 (100 mg, 0.49 mmol), 3-chloro-2-methylbenzenesulfonyl chloride (337 mg, 1.50 mmol) and sodium bicarbonate (126 mg, 1.50 mmol) was heated purely until it melted and heated Continue for 10 minutes. At room temperature the solid was extracted with ethyl acetate. The organic phase was dried (sodium sulfate), filtered and the solvent was evaporated. The residue was purified by flash chromatography on silica gel eluting with 30% acetone in DCM to give (84 mg, 43%) solid material: MS (ion spray, [M + H] ⁺ ) m / z 401; _{Anal for} C ₁₅ H ₁₆ CIN ₃ 0 ₄ S _2. Theoretical value: found 44.8 (44.8)% H 4.0 (4.3)% N 10.4 (9.9)%.
[1635] Example 210L
[1636] 3-chloro-2-methyl-N- {4- [3- (3-oxo-4-morpholinyl) propyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1637] To a solution of Example 208B (187 mg, 0.44 mmol) in H ₂ 0 (2 mL) / THF (1 mL), chloroacetyl chloride (110 mg, 0.97 mmol) in THF (3 mL) was added dropwise over a period of 40 minutes. . The temperature was maintained at 8 ° C. and the pH was adjusted to about 6-8 by adding 2 M KOH continuously. Aqueous potassium hydroxide (6 M, 0.38 mL, 1.41 mmol) was added and the mixture was stirred at rt for 20 min. The pH was adjusted to 8 and the mixture was extracted with ethyl acetate. The organic phase was separated and the solvent was evaporated. The residue by flash chromatography on silica gel eluting with 30% acetone in DCM, to give the title compound 98mg (52%): MS (ion ^{spray, [MtH] +) m /} z 429. C l7 H 20 Analysis of ClN ₃ 0 ₄ S _2. Theoretical value: found C 47.5 (47.4)% H 4.7 (4.9)% N 9.8 (9.5)%.
[1638] Example 210M
[1639] 3-chloro-N, 2-dimethyl-N- {4-12- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1640] To a solution of Example 210A (100 mg, 0.24 mmol) and N-ethyldiisopropylamine (31 mg, 0.24 mmol) in DMF (3 mL) was added iodomethane (34 mg, 0.24 mmol). The mixture was stirred at rt for 2 h and then extracted with ethyl acetate. The organic phase was dried over sodium sulphate, filtered and the solvent was evaporated to give a solid. The solid was boiled in ethanol and then filtered to give 38 mg (37%) of the title compound: ^l H NMR (DMSO) δ 2.65 (s, 3H), 2.83 (t, 2H), 3.34 (t, 3H), 3.50 ( s, 3H), 3.54 (t, 2H), 3.78 (t, 2H), 3.93 (s, 2H), 6.63 (s, 1H), 7.37 (t, 1H), 7.66 (d, 1H), 7.90 (d , 1H); MS (ion spray, [M + H] ⁺ ) m / z 429.
[1641] Example 21 ON
[1642] 3-chloro-2-methyl-N- {4- [2- (2-methyl-3-oxo-4-morpholinyl) ethyll-1,3-thiazol-2-yl} benzenesulfonamide
[1643] Example 208 (0.250 g, 0.665 mmol) was stirred at 5 ° C. in THF (3 mL) and water (2 mL). While adjusting the pH to about 8 with aqueous potassium hydroxide (50%), 2-chloropropionic acid chloride was added neatly (10 x 16 pL). When acylation is complete (monitored by HPLC), the pH is adjusted to 14-15 with aqueous KOH resulting in ring closure. The reaction mixture was extracted with ethyl acetate (3 x 25 mL) and the combined organic phases were dried over magnesium sulfate. The solvent was removed and purified by silica gel chromatography (gradient of 2-4% methanol in DCM) to give the product as a white solid (0.120 g, 41% yield): HRMS for C ₁₇ H ₂₀ ClN ₃ O ₄ S ₂ Theoretical (act) m / z 429.0584 (429. 0581).
[1644] Example 210O
[1645] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] acetamide
[1646] Starting from Example 200A (100 mg, 0.30 mmol), acetic anhydride (37 mg, 0.36 mmol) and pyridine (3 mL), the synthesis was carried out using Method A to purify 85 mg (76%) of the title compound after purification. Obtained: MS (ion spray, [M + H] ⁺ ) m / z 373; Anal for C ₁₄ H _l6 ClN ₃ 0 ₃ S _2. Theoretical value: found C 45.0 (44.3)% H 4.3 (4.4)% N 11.2 (11. 0)%.
[1647] Example 210Q
[1648] 3-chloro-2-methyl-N- {4-12- (3-oxo-1,4-oxazepan-4-yl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1649] Intermediate 22 (0.133 g, 0.389 mmol) was dissolved in DCM: TFA (1: 1; 9 mL) and stirred for 25 minutes. The solvent was evaporated and the oil (0.250 g) was dissolved in DCM (25 mL) and washed with aqueous NaOH (2M, 2 mL). The organic phase was dried over magnesium sulphate and concentrated in vacuo to give an oil which was taken up in DCM (3 mL). DMAP (45 mg, 0.35 mmol, 1.6 eq) and 3-chloro-2-methylbenzenesulfonyl chloride (0.094 g, 0.44 mmol, 2 eq.) Were added. The reaction mixture was stirred overnight. The solvent was removed and the residue was purified by chromatography on silica gel (gradient of 1% to 2% methanol in DCM) in vacuo to yield the title compound as a white solid (27 mg, 28% yield): HRMS theoretical C ₁₇ H ₂₀ CIN ₃ 0 ₄ S ₂ m / z 429.0662 (429.0568).
[1650] Example 21 OR
[1651] 3-chloro-2-methyl-N- {4- [2- (2-oxo-1-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1652] Example 200A (200 mg, 0.60 mmol), ethyl 4-bromobutyrate (118 mg, 0.60 mmol), DIEA (156 mg, 1.20) and potassium iodide (10 mg, 0.06 mmol) in ethanol (5 mL) / DMSO (2 mL) ) Was refluxed overnight, cooled to room temperature and extracted with ethyl acetate. The organic phase was separated, dried over sodium sulphate, filtered and the solvent was evaporated. Purification of the residue by flash chromatography on silica gel eluting with 20% acetone in DCM gave 18 mg (7%) of solid material: ^l H NMR (CDC1 ₃ ) δ 2.00 (qn, 2H), 2.38 ( t, 2H), 2.65 (s, 3H), 2.88 (t, 2H), 3.40 (t, 2H), 3.58 (t, 2H), 6.24 (s, 1H), 7.22 (t, 1H), 7.52 (dd , 1H), 8.01 (dd, 1H); MS (ion spray, [M + H] ⁺ ) m / z 399.
[1653] Example 210S
[1654] 3-chloro-2-methyl-N- {4- [2- (2-oxo-1-imidazolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1655] Example 191A (6.5 g, 15.8 mmol) was added dropwise to 1,2-ethanediamine (25 mL) in THF (6 mL) at 5 ° C. The mixture was stirred at ambient temperature for 1 hour and then concentrated in vacuo. The residue was dissolved in MeOH (10 mL) and added dropwise to water (400 mL) at 0 ° C. The pale orange yellow precipitate was filtered off, dried (5.0 g, 84% yield) and used in the next step without further purification. The crude intermediate (0.381 g, 1.01 mmol) was stirred in THF (8 mL) at 0 ° C. and bis (trichloromethyl) carbonate (0.340 g, 1.1 mmol) in THF (2 mL) was added. The mixture was cooled to -10 ° C and triethylamine (0.268 g, 2.5 mmol) in THF (3 mL) was added slowly at -10 ° C. The mixture was stirred at 0 ° C. for 1.5 h and then warmed to rt. Stirring was continued for 40 minutes. Water (5 mL) was added and the resulting mixture was extracted with ethyl acetate (3 x 20 mL). The combined organic phases were dried (magnesium sulfate) and removed in vacuo to yield a residue, which was purified by reverse phase HPLC. This process 9mg of the title compound were obtained as a white solid: HRMS Calcd (found) m / z 400.0431 (400.0414) for _{C l5 H l7 ClN 4 0 2} S 2
[1656] Example 210T
[1657] 3-chloro-2-methyl-N- {4-12- (2-oxo-1,3-oxazolidin-3-yl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1658] To a solution of Example 208A (0.490 g, 1. 45 mmol) in THF (6 mL) was added N, N 'carbonyl dimidazole (0.194 g, 1.2 mmol) at 0 ° C. The reaction mixture was cooled to -10 ° C and triethylamine (0.400 g, 4 mmol) in THF (3 mL) was added slowly at -10 ° C. Ethyl acetate (50 mL) was added and the resulting solution was washed with 0.25 M HCL (2 × 15 mL), brine (30 mL) and dried over magnesium sulfate. Purification of the crude material after removal of the solvent by reverse-phase HPLC, to give the product as a white solid (0.080g, 14% yield): HRMS for C _l6 H _l5 ClN ₃₀₄ S ₂ Calcd (found) m / z 401.0271 (401 0260).
[1659] Example 210U
[1660] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N- (2 hydroxyethyl) -2- Furamide
[1661] A mixture of Example 208A (131 mg, 0.3 mmol), aqueous sodium carbonate (10%, 2 mL) in THF (5 mL) was treated with furoyl chloride (117 mg, 0.9 mmol) in THF (1 mL) at 0 ° C. . The reaction mixture was warmed to room temperature and stirred overnight. Ethyl acetate (20 mL) was added and the mixture was washed with water, dried (sodium sulfate) and evaporated to give an oil residue. Purification by flash column chromatography on silica gel eluting with an ethyl acetate / methanol mixture gave 51 mg (36%) of the title compound: ^l H NMR (DMSO) δ 2.66 (s, 3H), 2.78 (t, 2H), 3.52-3.61 (m, 4H), 3.74 (t, 2H), 6.45 (s, 1H), 6.52 (dd, 1H), 6.90 (d, 1H), 7.36 (t, 1H), 7.63 (dd, 1H) , 7.69 (br s, 1 H), 7.91 (dd, 1 H), 12.62 (br s, NH).
[1662] Example 210 UA
[1663] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N-methylcyclopropanecarboxamide
[1664] Synthesis was carried out at room temperature using Synthesis Method A, Example 200B (200 mg, 0.58 mmol), cyclopropanecarbonyl chloride (63 mg, 0.61 mmol) and pyridine (2 mL) to purify 125 mg (52%) The title compound was obtained: MS (ion spray, [M + H] ⁺ ) m / z 414; _{C l7 H 20 ClN 3 0 3} S 2 · H ₂ 0 Calcd analysis of 0.5 (measured value):. C 48.4 (48.5) % H 5.0 (5.2)% N 9. 9 (9.6)%.
[1665] Example 210V
[1666] 3-chloro-2-methyl-N- {4- [2- (4-methyl-2-oxo-1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride
[1667] Example 191 A (600 mg, 1.46 mmol), N-BOC-ethylenediamine (469 mg, 2.93 mmol) and a mixture of DIEA (189 mg, 1.46 mmol) were refluxed in ethanol (10 mL) for 3 hours. 265 mg (38%) intermediate tert-butyl 2- {[2- (2-{[(3-chloro-2) by evaporation of the solvent and flash chromatography on Si0 ₂ eluting with 10% methanol in DCM -Methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] amino} ethylcarbamate. This material (255 mg, 0.54 mmol) was dissolved in DCM (4 mL) followed by the addition of DMAP (163 mg, 1.21 mmol). Chloroacetyl chloride (134 mg, 1.18 mmol) dissolved in DCM (2 mL) was added and the mixture was stirred at rt for 1 h and then washed with aqueous HC1 (2 M). The remaining organic phase was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was taken up in ethyl acetate (25 mL) and bubbled HC1 at 0 ° C. for 3 minutes. The mixture was stirred for 10 minutes and the solvent was evaporated to give 284 mg of N- (2-aminoethyl) -2-chloro-N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] acetamide hydrochloride was obtained. This material (280 mg, 0.57 mmol) and sodium bicarbonate (169 mg, 2.01 mmol) were refluxed in ethanol (30 mL) for 2 hours. The solvent was evaporated and the residue was flash chromatographed on a gradient of RP silica gel eluting with (acetonitrile in H ₂ 0/1% concentrated HC 1) to 113 mg (47%) of 3-chloro-2-methyl-N {4- [2- (2-oxo-1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride was obtained. Sodium cyanaborohydride (24 mg) in a solution of this material (113 mg, 0.27 mmol), 37% aqueous formaldehyde (38 uL, 1.36 mmol), 5M HC1 / methanol (22 uL, 0.11 mmol) in methanol (10 mL). , 0.38 mmol) was added. The mixture was stirred at rt for 1 h. RP silica gel flash was evaporated the solvent and the residue was eluted with a gradient (acetonitrile in H ₂ 0/1% concentrated HC 1) to give 69 mg (59%) of the title compound: MS (ion spray, [M + H ] ⁺ ) m / z 428. Analysis for C ₁₇ H ₂₁ ClN ₄ O ₃ S ₂ .1 HCl. Theoretical value: found 43.9 (43.5)% H 5. 2 (4.9)% N 12.0 (11.9) )%.
[1668] Example 210W
[1669] 3-chloro-2-methyl-N- (4- {2-[(methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide
[1670] Using Method A, the synthesis was carried out with Example 200A (100 mg, 0.30 mmol), methanesulfonyl chloride (42 mg, 0.36 mmol) and pyridine (3 mL) to purify 85 mg (69%) of the title compound after purification. Obtained: MS (ion spray, [M + H] ⁺ ) m / z 409; Anal for C ₁₃ H ₁₆ ClN ₃ O ₄ S _3. Theoretical value: found C 38. 1 (38. 5)% H 3. 9 (4. 1)% N 10. 2 (9. 9)%.
[1671] Example 210X
[1672] 3-chloro-2-methyl-N- (4- {2- [methyl (methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide
[1673] Example 200B (81 mg, 0.23 mmol), methanesulfonyl chloride (60 mg, 0. 52 mmol) and pyridine (2 mL) were synthesized at room temperature according to Method A to give 31 mg (28%) of the title compound. Obtained: ¹ H NMR (CDC1 ₃ ) δ 2. 63 (s, 3H), 2. 77 (s, 3H), 2. 87 (s, 3H), 3. 02 t, 2H), 3. 44 ( t, 2H), 6. 34 (s, 1H), 7. 24 (t, 1H), 7. 55 (dd, 1H), 8. 00 (dd, 1H); MS (ion spray, [M + H] ⁺ ) m / z 423.
[1674] Example 210Y
[1675] 3-chloro-2-methyl-N- [4- (2-{[(trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide
[1676] Trifluoromethanesulfone anhydride (128 mg, 0. 45 mmol) dissolved in DCM (1 mL) was added to Example 200A (150 mg, 0.) of DCM (15 mL) and TEA (46 mg, 0. 45 mmol) at room temperature. 45 mmol) in solution. The mixture was stirred for 1 hour and the solvent was evaporated. The crude material was purified by flash chromatography on silica gel eluting with 10% acetone in DCM to give 100 mg (48%) of solid material: MS (ion spray, [M + H] ⁺ ) m / z 463. Analysis for C ₁₃ H ₁₃ ClF ₃ N ₃ O ₄ S _3. Theoretical value: found C 33. 7 (34.0)% H 2. 8 (2.9)% N 9. 1 (9.0)
[1677] Example 210Z
[1678] 3-chloro-2-methyl-N- {4-2- {methyl [(trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide
[1679] Trifluoromethanesulfone anhydride (123 mg, 0. 43 mmol) dissolved in DCM (1 mL) was added to Example 200B (150 mg, 0. 43) in DCM (25 mL) and TEA (44 mg, 0. 43 mmol) at room temperature. mmol) solution. The mixture was stirred overnight and the solvent was evaporated. The crude material was purified by flash chromatography on silica gel eluting with 10% acetone in DCM to give 110 mg (53%) of solid material: MS (ion spray, [M + H] ⁺ ) m / z 477. Analysis for C ₁₄ H ₁₅ ClF ₃ N ₃ 0 ₄ S _3. Theoretical value: found C 35. 2 (35. 3)% H 3.2 (3.1)% N 8.8 (8.5)%.
[1680] Example 210ZA
[1681] N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -1-methyl-lH-amidazole-4- Sulfonamide
[1682] A suspension of Example 200A (200 mg, 0.60 mmol), 1-methylamidazole-4- sulfonyl chloride (109 mg, 0.60 mmol), TEA (61 mg, 0.60 mmol) in DCM (10 mL) was refluxed for 1 hour. The reaction mixture was cooled to room temperature and the solid was filtered off to afford 161 mg (58%) of the pure title compound: MS (ion spray, [M + H] ⁺ ) m / z 476; Analysis of C ₁₆ H ₁₈ ClN ₅ O ₄ S _3. Theoretic (act): C 40.4 (40.2)% H 3. 8 (3.8)% N 14.7 (14.6)%.
[1683] Example 210ZB
[1684] 3-chloro-N- (4- {2-[[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] ethyl} -1,3-thiazol-2-yl) -2-methylbenzene Sulfonamide
[1685] Using Method A at room temperature, the synthesis was carried out with Example 200B (150 mg, 0.43 mmol), 3-chloro-2-methylbenzenesulfonyl chloride (117 mg, 0. 52 mmol) and pyridine (2 mL), After purification 91 mg (39%) of the title compound were obtained: MS (ion spray, [M + H] ⁺ ) m / z 533; Analysis for C _{2 O} H ₂₁ C1 ₂ N ₃ 0 ₄ S _3. Theoretical value: found 44.5 (45.4)% H 4.0 (4.1)% N 7.9 (7.7)%.
[1686] Example 213A
[1687] N- [4- (2-bromoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide
[1688] Ice-cooled mixture of Example 181A (2.03 g, 6.10 mmol), triphenylphosphine (4.80 g, 18.31 mmol) and carbon tetrabromide (6.07 g, 18.31 mmol) in DMF (30 mL) for 1.5 h Stir and then pour into water. The mixture was extracted with DCM, dried (sodium sulfate) and the solvent was evaporated. The crude material was purified twice by flash chromatography on silica gel gradient eluted with 0-4% acetone in DCM to give N- [4- (2-bromoethyl) -1, as a solid (990 mg, 41%). 3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide was obtained. MS (ion spray, [M + H] ⁺ ) m / z 394; Anal for C ₁₂ H ₁₂ BrClN ₂ O ₂ S _2. Theoretical found: C 36.4 (36.6)% H 3.1 (3.3)% N 7.1 (7.2)%.
[1689] Example 214A
[1690] 3-chloro-N- [4- (2-chloroethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide
[1691] A mixture of Example 181A (100 mg, 0.30 mmol), triphenylphosphine (158 mg, 0.60 mmol) and carbon tetrachloride (116 mg, 0.75 mmol) in DMF (2 mL) was stirred overnight and then poured into water. The mixture was extracted with EtOAc, dried (sodium sulfate) and the solvent was evaporated. The crude material was purified by flash chromatography on silica gel gradient eluted with 2-4% acetone in DCM to give a solid (25 mg, 24%). _{^{l H NMR (CDC1 3) δ}} 2. 64 (s, 3H), 3.17 (t, 2H), 3.77 (t, 2H), 6.30 (s, 1H), 7.24 (m, 2H), 7.56 (d, 1H ), 8.02 (d, 1 H); MS (ion spray, [M + H] ⁺ ) m / z 350.
[1692] Example 223A
[1693] 3-chloro-2-methyl-N- {4-[(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1,3-thiazol-2-yl} benzenesulfonamide
[1694] Example 87A (367 mg, 1.06 mmol) was coupled with N-acetyl hydrazine (94 mg, 1.24 mmol) using Method F. After purification, 330 mg (94%) of intermediate hydrazide were obtained (mp 112 ° C.). This hydrazide (49 mg, 0.12 mmol) was suspended in acetonitrile (dry, 1 mL) in a Heck vial and treated with phosphorus oxychloride (100 L, 0.593 mmol). The vial was sealed and heated at 80 ° C. for 2 hours in an oil bath. Water (3 mL) was added and the extraction reaction was completed with ethyl acetate, dried (sodium sulfate), filtered and the volatiles were evaporated in a rotary evaporator to give a pale brown oil which crystallized from methanol. Pale brown crystals were obtained (17 mg, 36%): MS (ion spray, [M + H] ⁺ ) m / z 385.
[1695] Example 231B
[1696] Ethyl 3- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) propanoate
[1697] Thiourea (4.86 g, 64 mmol) was dissolved in ethanol (60 mL) at 60 ° C. Methyl levulinate (4.16 g, 32 mmol) and iodine (8.11 g, 32 mmol) were added and the temperature was raised to reflux. The mixture was stirred for 6 hours and the solvent was evaporated. Ethyl acetate, water and sodium bicarbonate solution were added and the mixture was extracted. The organic phase was dried (sodium sulfate), filtered and the solvent was evaporated to give 6 g crude product. The crude was flash chromatographed in Si0 ₂ eluting with 5% methanol in DCM to give ethyl 3- (2-amino-1, 3-thiazol-4-yl) propanoate (1.33 g, 7.14 mmol, 11%). Got. This material (1.23 g, 6.14 mmol) was sulfonylated with 3-chloro-2-methylbenzenesulfonyl chloride (1.79 g, 7. 98 mmol) in pyridine (5 mL) according to Method A, yielding 1.91 g (80%). ) Was obtained: MS (ionspray, [M + H] ⁺ ) m / z 388. Anal. For C ₁₅ H _l7 ClN ₂ 0 ₄ S _2. Theoretical value: found C 46.3 (46.3)% H 4.4 (4.5)% N 7.2 (7.0)%.
[1698] While various embodiments of the invention have been described above, those skilled in the art further realize further secondary variations within the scope of the invention. The scope of the invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents.

权利要求:
Claims (12)
[1" claim-type="Currently amended] A compound of formula II or a salt, hydrate or solvate thereof.
Formula II

Wherein T is an aryl ring or heteroaryl ring or aryl-C ₂ -alkenyl ring, optionally independently substituted by [R] n, where n is an integer 0-5 and R is hydrogen, aryl, hetero Aryl, heterocyclic ring, optionally halogenated C _1-6 -alkyl, optionally halogenated C _1-6 -alkoxy, C _1-6 -alkylsulfonyl, carboxy, cyano, nitro, halogen, optionally mono- Or di-substituted amines, optionally mono- or di-substituted amides, aryloxy, arylsulfonyl, arylamino, wherein the aryl, heteroaryl and aryloxy moieties and heterocyclic rings are more optionally at one or more positions independently of each other C _1-6 - acylamino, C _1-6 - alkylthio, cyano, nitro, hydrogen, halogen, optionally halogenated C _l-6-alkyl, optionally halogenated C _1-6 - alkoxy, optionally Mono- or di-substituted amides with (benzoyl) No) methyl, carboxy, 2-thienylmethylamino or ({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) Can;
Provided that when R ¹ is H, X is CH ₂ , Y is CO, R ² is EtO and B is H, then T is 2,4-dichloro-5-methylphenyl, 4-chlorophenyl, 4-chloro -2,5-dimethylphenyl, 2,4-difluorophenyl, 3-nitrophenyl and phenyl;
R ¹ is hydrogen or C _1-6 -alkyl;
X is CH ₂ or CO;
Y is CH ₂ , CO or a single bond;
B is hydrogen, C _1-6 -alkyl or dimethylaminomethyl;
R ² is C _1-6 -alkyl, azido, arylthio, heteroarylthio, halogen, hydroxymethyl, 2-hydroxyethylaminomethyl, methylsulfonyloxymethyl, 3-oxo-4-morpholinolinyl Methylene, C _1-6 -alkoxycarbonyl, 5-methyl-1,3,4-oxadiazol-2-yl;
NR ³ R ⁴ , wherein R ³ and R ⁴ are each independently hydrogen, C _1-6 -alkyl, optionally halogenated C _1-6 -alkylsulfonyl, C _1-6 -alkoxy, 2-methoxyethyl, 2 -Hydroxyethyl, 1-methylimidazolylsulfonyl, C _1-6 -acyl, cyclohexylmethyl, cyclopropanecarbonyl, aryl, optionally halogenated arylsulfonyl, furylcarbonyl, tetrahydro-2-furanyl Methyl, N-carbetoxypiperidyl, or C _1-6 -alkyl substituted with one or more aryl or heteroaryl, or
NR ³ R ⁴ is amidazole, piperidine, pyrrolidine, piperazine, morpholine, oxazepine, oxazole, thiomorpholine, 1,1-dioxidothiomorpholine, 2- (3,4- Dihydro-2 (1H) isoquinolinyl), (1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept-5-yl, together with Heterocyclic systems may be optionally substituted by C _1-6 -alkyl, C _1-6 -acyl, hydroxy, oxo, t-butoxycarbonyl;
OCONR ³ R ⁴ , wherein R ³ and R ⁴ are each independently selected from hydrogen, C _1-6 -alkyl or together form morpholinyl;
R ⁵ 0, wherein R ⁵ is hydrogen, optionally halogenated C _1-6 -alkyl, aryl, heteroaryl, C _1-6 -acyl, C _1-6 -alkylsulfonyl, arylcarbonyl, heteroarylcarbonyl, 2-carbomethoxyphenyl.
[2" claim-type="Currently amended] The method of claim 1,
T is 5-chloro-1,3-dimethyl-lH-pyrazol-4-yl; 4-chloro-2,3,1-benzoxadiazolyl; 5- (dimethylamino) -1-naphthyl; 1-methylimidazol-4-yl; 1-naphthyl;
2-naphthyl; (E) -2-phenylethenyl; 8-quinolinyl;
(Benzoylamino) methyl, bromo, chloro, 3-isoxazolyl, 2- (methylsulfanyl) -4-pyrimidinyl, 1-methyl-5- (trifluoromethyl) pyrazol-3-yl, Thienyl substituted with one or more of phenylsulfonyl and pyridyl;
Acetylamino, 3-acetylaminophenyl, 3-acetylphenyl, benzeneamino, 1,3-benzodioxol-5-yl, 2-benzofuryl, benzylamino, 3,5-bis (trifluoromethyl) phenyl, Bromo, butoxy, carboxy, chloro, 4-carboxyphenyl, 3-chloro-2-cyanophenoxy, 4-chlorophenyl, 5-chloro-2-thienyl, cyano, 3,4-dichlorophenyl, ({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl), fluoro, 5-fluoro-2-methoxyphenyl, 2- Furyl, hydrogen, iodo, isopropyl, methanesulfonyl, methoxy, methyl, 4-methyl-l-piperazinyl, 4-methyl-l-piperidinyl, 4-methylsulfanylphenyl, 5-methyl- 2-thienyl, 4-morpholinyl, nitro, 3-nitrophenyl, phenoxy, phenyl, n-propyl, 4-pyridyl, 3-pyridylmethylamino, 1-pyrrolidinyl, 2-thienyl, Substituted with one or more of 3-thienyl, 2-thienylmethylamino, trifluoromethoxy, 4-trifluoromethoxyphenyl, trifluoromethyl Selected from phenyl or; or
Provided that when R ¹ is H, X is CH ₂ , Y is CO, R ² is EtO and B is H, then T is 2,4-dichloro-5-methylphenyl, 4-chlorophenyl, 4-chloro -2,5-dimethylphenyl, 2,4-difluorophenyl, 3-nitrophenyl and phenyl;
R ¹ is hydrogen or methyl;
X is CH ₂ or CO;
Y is CH ₂ , CO or a single bond;
B is hydrogen, methyl or dimethylaminomethyl;
R ² is n-propyl, azido, bromo, chloro, 2-pyridinylsulfanyl, 3-oxo-4-morpholinolinyl methylene, ethoxycarbonyl, 5-methyl-1,3,4-oxa Diazol-2-yl, hydroxymethyl, 2-hydroxyethylaminomethyl, methylsulfonyloxymethyl;
NR ³ R ⁴ , wherein R ³ and R ⁴ are each independently acetyl, benzhydryl, 1,3-benzodioxol-5-ylmethyl, benzyl, 3-chloro-2-methylphenylsulfonyl, cyclohexyl, cyclo Hexylmethyl, cyclopropanecarbonyl, ethyl, 2-furylcarbonyl, 2-furylmethyl, hydrogen, 2-hydroxyethyl, 2- (lH-indol-3-yl) ethyl, isopropyl, methoxy, 2- Methoxyethyl, methyl, 4- (1-methylimidazolyl) sulfonyl, methylsulfonyl, phenyl, (1S) -phenylethyl, n-propyl, tetrahydro-2-furanylmethyl, trifluoromethylsul Fonyl, N-carbetoxypiperidyl; or
NR ³ R ⁴ together are 4-acetylpiperazinyl, 4-t-butoxycarbonylpiperazinyl, 2- (3, 4-dihydro-2 (1H) isoquinolinyl); (2R, 6S) -2, 6-dimethylmorpholinyl, (2R) -2,4-dimethyl-1-piperazinyl, 2-hydroxy-3-oxomorpholinyl, imidazolyl, 2-methyl -3-oxomorpholinyl, 4-methyl-2-oxopiperazinyl, 4-methylpiperazinyl, morpholinyl, (1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept -5-yl, 2-oxoimidazolinyl, 3-oxomorpholinyl, 3-oxo-1, 4-oxazinyl, 2-oxooxazolinyl, piperazinyl; Piperidinyl; Pyrrolidinyl; Pyrrolidoneyl, thiomorpholinyl; 1, 1-dioxido-thiomorpholinyl;
OCONR ³ R ⁴ , wherein R ³ and R ⁴ are each independently selected from ethyl, hydrogen or together form morpholinyl;
R ⁵ 0, where R ⁵ is acetyl, benzoyl, benzyl, ethyl, 2-fluoroethyl, 2-furylcarbonyl, hydrogen, isobutyryl, isopropyl, methyl, 2-carbomethoxyphenyl, methylsulfonyl, Phenyl, propionyl, 3-pyridinyl, 2,2,2-trifluoroethyl.
[3" claim-type="Currently amended] The method according to claim 1 or 2,
A compound characterized in that it is selected from the group consisting of:
Ethyl 2- (2-(((4-methylphenyl) sulfonyl) amino) -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-{[(2, 5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-{[(3-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-isopropylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[3-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino)- 1,3-thiazol-4-yl] acetate,
Ethyl [2-({[4-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino)- 1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[2- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-({[3- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-({[4- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl 2- (2-{[(4-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2, 4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(5-fluoro-2-methylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-methoxy-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3,5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(3,4-dichlorophenyl) sulfonyl amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-([(4-butoxyphenyl) sulfonyl] amino] -1,3-thiazol-4-yl) acetate,
Ethyl (2- [(4-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2- ({[4- (acetylamino) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl {2-[(8-quinolinylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl (2-{[(3,4-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-iodophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-chloro-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({5- (dimethylamino) -1-naphthyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(1-methyl-1H-imidazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(5-bromo-2-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,5-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl {2-[(2-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl {2-[(methylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl (2-{[(3-bromo-5-chloro-2-thienyl) sulfonyl] amino] -1,3-thiazol-4-yl) acetate,
Ethyl {2-[(5-[(benzoylamino) methyl] -2-thienyl} sulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl {2-[({5- [l-methyl-5- (trifluoromethyl) -lH-pyrazol-3-yl] -2- thienyl} sulfonyl) amino] -1,3-thiazole -4-yl} acetate,
Ethyl (2-{[(4-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl {2-[({5- [2- (methylsulfanyl) -4-pyrimidinyl] -2-thienyl} sulfonyl) amino] -1,3 thiazol-4-yl} acetate,
Ethyl (2-{[(3-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4,5-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2 [{[(((E) -2-phenylethenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2,3,4-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-bromo-2, 5-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2, 3-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4,5-dichloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-{[(5- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2, 6-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (acetylamino) -3-chlorophenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(5-chloro-1,3-dimethyl-lH-pyrazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-bromo-5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- {2-[(l-naphthylsulfonyl) amino] -1, 3-thiazol-4-yl} acetate,
Ethyl (2-{[(2, 5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2- {[(4- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-{[(2- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(4-bromo-2-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,3,4-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(7-chloro-2,1,3-benzoxadiazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4,6-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
2-chloro-5-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} sulfonyl) -4-fluorobenzoic acid,
Ethyl (2-{[(5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-chloro-4-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[5- (3-isoxazolyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(4-bromo-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-phenoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-chloro-2, 6-dimethylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-{[(2-methyl-4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-({[2,4-bis (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl 2- [2-{[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl oxo (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) (oxo) acetate,
Ethyl oxo (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-{[(1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} (oxo) acetate,
Ethyl (2-{[(2, 4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) (oxo) acetate,
2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
2- (2-{[(2, 5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
(2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3 thiazol-4-yl) acetic acid,
Isopropyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Phenyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl {2-[([l, 1'-biphenyl] -4-ylsulfonyl) amino] -5-methyl-1,3-thiazol-4-yl} acetate,
Methyl (2-{[(4-chlorophenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
Methyl [2-{[(4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -5-methyl-1,3-thiazol-4-yl] acetate,
Methyl (5-methyl-2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl (5-methyl-2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl (2-{[((2,4-dichloro-6-methylphenyl) sulfonyl] amino} -5-methyl-1, 3-thiazol-4-yl) acetate,
N- (2-methoxyethyl) -2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(2,5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
N- (1,3-benzodioxol-5-ylmethyl) -2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
N- (2-furylmethyl) -2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
2- (2-{[(2,4-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
N-isopropyl-2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
N- [2- (lH-indol-3-yl) ethyl] -2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
N- (cyclohexylmethyl) -2- {2-[(phenylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide,
2- (2-{[(4-chlorophenyl) sulfonyl] amino) -1,3-thiazol-4-yl) -N- (2-furylmethyl) acetamide,
N-benzhydryl-2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N- (tetrahydro-2furanylmethyl) acetamide,
Ethyl 4-{[2- (2- {[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] amino} -1- piperidinecarboxylate,
N-benzhydryl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diethylacetamide,
2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diethylacetamide,
N, N-diethyl-2- (2-{[(4-propylphenyl) sulfonyl} amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(2, 4-dichloro-6-methylphenyl) sulfonyl] amino} -1, 3-thiazol-4-yl) -N, N-diethylacetamide,
N, N-diethyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- {2-[([l, 1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diisopropylacetamide,
N, N-diisopropyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiol-4-yl) acetamide,
2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diisopropylacetamide,
N, N-diisopropyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diisopropylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dipropylacetamide,
N-benzyl-2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
N-benzyl-2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dimethylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiol-4-yl) -N-cyclohexyl-N-methylacetamide,
3-chloro-N- {4- [2- (3,4-dihydro-2 (1H) -isoquinolinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2 Methylbenzenesulfonamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N-phenylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-isopropyl-N methylacetamide,
2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-isopropyl-N- methylacetamide,
N-ethyl-N-methyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N-methylacetamide,
N-ethyl-N-methyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-ethyl-N- methylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N methylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N [(1S) -1-phenylethyl] acet amides,
3-chloro-2-methyl-N- {4- [2-oxo-2- (1-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl benzenesulfonamide,
2,4,6-trichloro-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4,6-trichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
2, 4-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] 1,3-thiazol-2-yl} benzenesulfonamide,
4-chloro-2, 6-dimethyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-phenoxybenzenesulfonamide,
2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2, 4-bis (trifluoromethyl) benzenesulfonamide,
4-bromo-2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4- (2-furyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3'-fluoro-6'-methoxy-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1 ' -Biphenyl] -4-sulfonamide,
4- (5-methyl-2-thienyl) -N- [4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3'-acetyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4- Sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4 '-(trifluoromethoxy) [l, 1'-ratio Phenyl] -4-sulfonamide,
3 ', 4'-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
4- (1,3-benzodioxol-5-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzene Sulfonamide,
4- (5-chloro-2-thienyl) -N- [4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (4-pyridinyl) benzenesulfonamide,
N- {4 '-{[(4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [l, 1' ratio Phenyl] -3-yl} acetamide,
N- [4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (3 thienyl) benzenesulfonamide,
N- [4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (2 thienyl) benzenesulfonamide,
4 '-{[(4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [1, 1'-biphenyl] -4-carboxylic acid,
4 '-(methylsulfanyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, 1'-biphenyl ] -4-sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3 ', 5'-bis (trifluoromethyl) [l, l'-biphenyl] -4-sulfonamide,
4'-chloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl] -4- Sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -l, 3-thiazol-2-yl} -3'-nitro [l, l'-biphenyl] -4- Sulfonamide,
4- (1-benzofuran-2-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (1-pyrrolidinyl) benzenesulfonamide,
4- (4-methyl-1-piperidinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
A-anilino-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4- (benzylamino) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(2-thienylmethyl) amino] benzenesulfonamide,
4- (4-morpholinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4- (4-methyl-l-piperazinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(3 pyridinylmethyl) amino] benzenesulfonamide,
2,4-dichloro-6-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4 sulfonamide ,
2,4,6-trichloro-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-N- (4- {2-[(2R, 6S) -2,6-dimethylmorpholinyl] -2-oxoethyl} -1,3-thiazol-2-yl)
2-methylbenzenesulfonamide, 3-chloro-2-methyl-N- (4- {2-[(1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept-5-yl]- 2-oxoethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl] benzenesulfonamide,
N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4- sulfonamide,
N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
2,4-dichloro-6-methyl-N- [4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4,6-trichloro-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (1,1-dioxido-4-thiomorpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
Tert-butyl 4-[(2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] -piperazinecarboxylate,
N- {4- [2- (4-acetyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3-chloro-2- methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluor Low Acetate,
3-chloro-2-methyl-N- {4- [2-oxo-2- (1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluoroacetate,
2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) Benzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
2,4-dichloro-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-N- (4- {2-[(2R) -2, 4-dimethylpiperazinyl] -2-oxoethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulphone amides,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methoxy-N-methylacetamide,
3-chloro-2-methyl-N- [4- (2-oxopentyl) -1,3-thiazol-2-yl] benzenesulfonamide,
4-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
3-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- [4- (3-hydroxypropyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-isopropoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
N- {4- [2- (benzyloxy) ethyl] -1,3-thiazol-2-yl} -3-chloro-2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-methoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- {4- [2- (2-fluoroethoxy) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2, 2,2-trifluoroethoxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- [2-pyridinylsulfanyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (3-pyridinyloxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
Methyl 2- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethoxy] benzoate,
3-chloro-N- [5-[(dimethylamino) methyl] -4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl methanesulfonate,
3- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) propyl methanesulfonate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl acetate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl propionate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-methylpropanoate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-furoate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl benzoate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 4-morpholinecarboxylate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl diethylcarbamate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl ethylcarbamate,
N- [4- (2-azidoethyl) -1, 3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
N- [4- (2-aminoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (methylamino) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
3-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide hydrochloride,
3-chloro-N- {4- [2- (lH-imidazol-l-yl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide dihydrate,
3-chloro-2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) ethyl} -1,3-thiazol-2-yl} benzenesulfonamide dihydrochloride,
3-chloro-2-methyl-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
3-chloro-2-methyl-N- [4- (4-morpholinylmethyl) -1,3-thiazol-2-yl] benzenesulfonamide hydrochloride,
2,4,6-trichloro- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
2,4-dichloro-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide hydrochloride,
3-chloro-N- {4- [2- (ethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
3-chloro-N- (4- {2-[(2-hydroxyethyl) amino] ethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulfonamide,
3-chloro-N- (4-[(2-hydroxyethyl) amino] propyl} -1,3-thiazol-2-yl) -2-methylbenzenesulfonamide hydrochloride hydrate,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N-ethylacetamide,
3-chloro-2-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-N- {4- {2- (2-hydroxy-3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
2, 4-dichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4,6-trichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl) benzenesulfonamide,
4,5-dichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-thiophenesulfonamide,
N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -4-phenoxybenzenesulfonamide,
3-fluoro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -5- (2-pyridinyl) -2-thiophenesulfonamide,
N- {2-chloro-4-[({4- [2-83-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} amino) sulfonyl] phenyl} acetamide ,
3-chloro-2-methyl-N- {4-[(3-oxo-4-morpholinyl) methyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [3- (3-oxo-4-morpholinyl) propyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-N, 2-dimethyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-methyl-3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] acetamide,
3-chloro-2-methyl-N- {4- [2- (3-oxo-1,4-oxazepan-4-yl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-oxo-1-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-oxo-1-imidazolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-oxo-1,3-oxazolidin-3-yl) ethyl] -1,3-thiazol-2-yl} benzene sulfonamide ,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N- (2-hydroxyethyl) -2 -Furamide,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N-methylcyclopropanecarboxamide,
3-chloro-2-methyl-N- {4- [2- (4-methyl-2-oxo-1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride ,
3-chloro-2-methyl-N- (4- {2-[(methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
3-chloro-2-methyl-N- (4- {2- [methyl (methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
3-chloro-2-methyl-N- [4- (2-{[trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
3-chloro-2-methyl-N- [4- (2- {methyl [(trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -1- methyl-lH-amidazole-4- Sulfonamide,
3-chloro-N- (4- {2-[[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] ethyl} -1,3-thiazol-2-yl) -2-methylbenzene Sulfonamide,
N- [4- (2-bromoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-chloroethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4-[(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
Ethyl 3- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) propanoate.
[4" claim-type="Currently amended] 4. A compound according to any one of claims 1 to 3 for medical use.
[5" claim-type="Currently amended] A process for preparing a compound according to claim 1, characterized in that it comprises one or more of the following steps.
a) sulfonamide coupling by reacting 2-aminothiazole with sulfonylchloride in the presence of a base,
b) sulfonamide coupling by reacting a 2-aminothiazole derivative with sulfonylchloride in the presence of a base,
c) ester hydrolysis by treating the carboxylic acid ester with an aqueous hydroxide,
d) amide coupling by reacting a carboxylic ester with an amine,
e) amide coupling by reacting a carboxylic acid with an amine in the presence of EDCI,
f) amide coupling by reacting a carboxylic acid with an amine in the presence of EDCI, HOAT or HOBT
g) amide coupling by reacting a carboxylic ester with an amine in the presence of aluminum chloride,
h) formation of a thiazole ring by reacting an optionally substituted thiourea with α-haloketone,
i) forming thiazole ring by reacting thiourea with a ketone,
j) acylation of alcohols by reacting with acid chlorides in the presence of bases,
k) carbamoylation of alcohols by reacting with 4-nitrophenylchloroformate and then with primary or secondary amines,
1) palladium coupling of halo compound and boronic acid,
m) palladium coupling of a halo compound with an amine having 18-crown-6,
n) Palladium coupling of a halo compound with an amine free of 18-crown-6.
[6" claim-type="Currently amended] Diabetes, Syndrome X, Obesity, Glaucoma, Hyperlipidemia, Hyperglycemia, Osteoporosis, comprising administering an effective amount of a compound of Formula II or a salt, hydrate or solvate thereof to a mammal, including a person in need thereof , For the treatment or prevention of tuberculosis, dementia, depression, viral diseases and inflammatory disorders.
Formula II

Wherein T is an aryl ring or heteroaryl ring or aryl-C ₂ -alkenyl ring, optionally independently substituted by [R] n, where n is an integer 0-5 and R is hydrogen, aryl, hetero Aryl, heterocyclic ring, optionally halogenated C _1-6 -alkyl, optionally halogenated C _1-6 -alkoxy, C _1-6 -alkylsulfonyl, carboxy, cyano, nitro, halogen, optionally mono- Or di-substituted amines, optionally mono- or di-substituted amides, aryloxy, arylsulfonyl, arylamino, wherein the aryl, heteroaryl and aryloxy moieties and heterocyclic rings are more optionally at one or more positions independently of each other C _1-6 - acylamino, C _1-6 - alkylthio, cyano, nitro, hydrogen, halogen, optionally halogenated C _l-6-alkyl, optionally halogenated C _1-6 - alkoxy, optionally Mono- or di-substituted amides with (benzoyl) No) methyl, carboxy, 2-thienylmethylamino or ({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) Can;
R ¹ is hydrogen or C _1-6 -alkyl;
X is CH ₂ or CO;
Y is CH ₂ , CO or a single bond;
B is hydrogen, C _1-6 -alkyl or dimethylaminomethyl;
R ² is C _1-6 -alkyl, azido, arylthio, heteroarylthio, halogen, hydroxymethyl, 2-hydroxyethylaminomethyl, methylsulfonyloxymethyl, 3-oxo-4-morpholinolinyl Methylene, C _1-6 -alkoxycarbonyl, 5-methyl-1,3,4-oxadiazol-2-yl;
NR ³ R ⁴ , wherein R ³ and R ⁴ are each independently hydrogen, C _1-6 -alkyl, optionally halogenated C _1-6 -alkylsulfonyl, C _1-6 -alkoxy, 2-methoxyethyl, 2 -Hydroxyethyl, 1-methylimidazolylsulfonyl, C _1-6 -acyl, cyclohexylmethyl, cyclopropanecarbonyl, aryl, optionally halogenated arylsulfonyl, furylcarbonyl, tetrahydro-2-furanyl Methyl, N-carbetoxypiperidyl, or C _1-6 -alkyl substituted with one or more aryl or heteroaryl, or
NR ³ R ⁴ is amidazole, piperidine, pyrrolidine, piperazine, morpholine, oxazepine, oxazole, thiomorpholine, 1,1-dioxidothiomorpholine, 2- (3,4- Dihydro-2 (1H) isoquinolinyl), (1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept-5-yl, together with Heterocyclic systems may be optionally substituted by C _1-6 -alkyl, C _1-6 -acyl, hydroxy, oxo, t-butoxycarbonyl;
OCONR ³ R ⁴ , wherein R ³ and R ⁴ are each independently selected from hydrogen, C _1-6 -alkyl or together form morpholinyl;
R ⁵ 0, wherein R ⁵ is hydrogen, optionally halogenated C _1-6 -alkyl, aryl, heteroaryl, C _1-6 -acyl, C _1-6 -alkylsulfonyl, arylcarbonyl, heteroarylcarbonyl, 2-carbomethoxyphenyl.
[7" claim-type="Currently amended] The method of claim 6,
T is 5-chloro-1,3-dimethyl-lH-pyrazol-4-yl; 4-chloro-2,3,1-benzoxadiazolyl; 5- (dimethylamino) -1-naphthyl; 1-methylimidazol-4-yl; 1-naphthyl;
2-naphthyl; (E) -2-phenylethenyl; 8-quinolinyl;
(Benzoylamino) methyl, bromo, chloro, 3-isoxazolyl, 2- (methylsulfanyl) -4-pyrimidinyl, 1-methyl-5- (trifluoromethyl) pyrazol-3-yl, Thienyl substituted with one or more of phenylsulfonyl, pyridyl;
Acetylamino, 3-acetylaminophenyl, 3-acetylphenyl, benzeneamino, 1,3-benzodioxol-5-yl, 2-benzofuryl, benzylamino, 3,5-bis (trifluoromethyl) phenyl, Bromo, butoxy, carboxy, chloro, 4-carboxyphenyl, 3-chloro-2-cyanophenoxy, 4-chlorophenyl, 5-chloro-2-thienyl, cyano, 3,4-dichlorophenyl, ({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl), fluoro, 5-fluoro-2-methoxyphenyl, 2- Furyl, hydrogen, iodo, isopropyl, methanesulfonyl, methoxy, methyl, 4-methyl-l-piperazinyl, 4-methyl-l-piperidinyl, 4-methylsulfanylphenyl, 5-methyl- 2-thienyl, 4-morpholinyl, nitro, 3-nitrophenyl, phenoxy, phenyl, n-propyl, 4-pyridyl, 3-pyridylmethylamino, 1-pyrrolidinyl, 2-thienyl, Substituted with one or more of 3-thienyl, 2-thienylmethylamino, trifluoromethoxy, 4-trifluoromethoxyphenyl, trifluoromethyl Selected from phenyl; or
R ¹ is hydrogen or methyl;
X is CH ₂ or CO;
Y is CH ₂ , CO or a single bond;
B is hydrogen, methyl or dimethylaminomethyl;
R ² is n-propyl, azido, bromo, chloro, 2-pyridinylsulfanyl, 3-oxo-4-morpholinolinyl methylene, ethoxycarbonyl, 5-methyl-1,3,4-oxa Diazol-2-yl, hydroxymethyl, 2-hydroxyethylaminomethyl, methylsulfonyloxymethyl;
NR ³ R ⁴ , wherein R ³ and R ⁴ are each independently acetyl, benzhydryl, 1,3-benzodioxol-5-ylmethyl, benzyl, 3-chloro-2-methylphenylsulfonyl, cyclohexyl, cyclo Hexylmethyl, cyclopropanecarbonyl, ethyl, 2-furylcarbonyl, 2-furylmethyl, hydrogen, 2-hydroxyethyl, 2- (lH-indol-3-yl) ethyl, isopropyl, methoxy, 2- Methoxyethyl, methyl, 4- (1-methylimidazolyl) sulfonyl, methylsulfonyl, phenyl, (1S) -phenylethyl, n-propyl, tetrahydro-2-furanylmethyl, trifluoromethylsul Fonyl, N-carbetoxypiperidyl; or
NR ³ R ⁴ together are 4-acetylpiperazinyl, 4-t-butoxycarbonylpiperazinyl, 2- (3, 4-dihydro-2 (1H) isoquinolinyl); (2R, 6S) -2, 6-dimethylmorpholinyl, (2R) -2,4-dimethyl-1-piperazinyl, 2-hydroxy-3-oxomorpholinyl, imidazolyl, 2-methyl -3-oxomorpholinyl, 4-methyl-2-oxopiperazinyl, 4-methylpiperazinyl, morpholinyl, (1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept -5-yl, 2-oxoimidazolinyl, 3-oxomorpholinyl, 3-oxo-1, 4-oxazinyl, 2-oxooxazolinyl, piperazinyl; Piperidinyl; Pyrrolidinyl; Pyrrolidoneyl, thiomorpholinyl; 1, 1-dioxido-thiomorpholinyl;
OCONR ³ R ⁴ , wherein R ³ and R ⁴ are each independently selected from ethyl, hydrogen or together form morpholinyl;
R ⁵ 0, where R ⁵ is acetyl, benzoyl, benzyl, ethyl, 2-fluoroethyl, 2-furylcarbonyl, hydrogen, isobutyryl, isopropyl, methyl, 2-carbomethoxyphenyl, methylsulfonyl, Phenyl, propionyl, 3-pyridinyl, 2,2,2-trifluoroethyl.
[8" claim-type="Currently amended] 8. A method according to claim 6 or 7, wherein the compound is selected from:
: Ethyl (2-{[(2,4-dichloro-5-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-[[(4-chlorophenyl) sulfonyl] amino] -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-{[(4-chloro-2,5-dimethylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2- {[(2,4-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-(((4-methylphenyl) sulfonyl) amino) -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-{[(2, 5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl 2- (2-{[(3-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-[(3-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-[(phenylsulfonyl) amino] -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-isopropylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[3-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino)- 1,3-thiazol-4-yl] acetate,
Ethyl [2-({[4-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino)- 1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[2- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-({[3- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-({[4- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl 2- (2-{[(4-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-[(2-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2, 4, 6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(5-fluoro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-methoxy-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3,5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(3,4-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-butoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (acetylamino) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl {2-[(8-quinolinylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl (2-{[(3,4-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-iodophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-chloro-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[5- (dimethylamino) -1-naphthyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[1-methyl-1H-imidazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(5-bromo-2-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2- {[(2, 5-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
ethyl. {2-[(2-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl {2-[(methylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl (2-{[(3-bromo-5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl {2-[({5-[(benzoylamino) methyl] -2-thienyl} sulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl {2-[({5- [l-methyl-5- (trifluoromethyl) -lH-pyrazol-3-yl] -2- thienyl} sulfonyl) amino] -1,3-thiazole -4-yl} acetate,
Ethyl (2-{[(4-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl {2-[({5- (2-methylsulfanyl) -4-pyrimidinyl] -2-thienyl} sulfonyl) amino] -1,3thiazol-4-yl} acetate,
Ethyl (2-{[(3-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4,5-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[(E) -2-phenylethenyl] sulfonyl] amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2,3,4-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-bromo-2, 5-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2, 3-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4,5-dichloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-({[5- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2,6-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (acetylamino) -3-chlorophenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(5-chloro-1,3-dimethyl-lH-pyrazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-bromo-5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl (2-{[(2, 5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-{[2- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(4-bromo-2-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,3,4-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(7-chloro-2,1,3-benzoxadiazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4,6-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
2-chloro-5-({4- (2-methoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} sulfonyl) -4-fluorobenzoic acid,
Ethyl (2-{[(5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-chloro-4-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[5- (3-isoxazolyl) -2-thienyl] sulfonyl} amino) -1, 3-thiazol-4-yl] acetate,
Ethyl (2-{[(4-bromo-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-phenoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[4-chloro-2, 6-dimethylphenyl) sulfonyl amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[2-methyl-4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-(([2,4-bis (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl 2- {2-[[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl oxo (2-[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) (oxo) acetate,
Ethyl oxo (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} (oxo) acetate,
Ethyl (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) (oxo) acetate,
2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
2- (2-{[(2,5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
(2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
Isopropyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Phenyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl 2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -5-methyl-1,3-thiazol-4-yl} acetate,
Methyl (2-{[(4-chlorophenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
Methyl [2-({[4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -5-methyl-1,3-thiazol-4-yl] acetate,
Methyl (5-methyl-2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl (5-methyl-2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
N- (2-methoxyethyl) -2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(2, 5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
N- (1,3-benzodioxol-5-ylmethyl) -2- {2- [(l-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
N- (2-furylmethyl) -2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
2- (2-{[(2,4-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
N-isopropyl-2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
N- [2- (1H-indol-3-yl) ethyl] -2- {2- [1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
N- (cyclohexylmethyl) -2- {2-[(phenylsulfonyl) amino] -1,3-thiazol-4-yl] acetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide,
2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N- (2furylmethyl) acetamide,
N-benzhydryl-2- (2- {[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N- (tetrahydro-2furanylmethyl) acetamide,
Ethyl 4-{[2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] amino} -1 piperidinecarboxylate,
N-benzhydryl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diethylacetamide,
2- {2- [([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diethylacetamide,
N, N-diethyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diethylacetamide,
N, N-diethyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- {2-[([1-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diisopropylacetamide,
N, N-diisopropyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2- {[(2, 4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N- diisopropylacetamide,
N, N-diisopropyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl amino} -1,3-thiazol-4-yl) acetamide,
2- (2-[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diisopropylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dipropylacetamide,
N-benzyl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
N-benzyl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N ethylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dimethylacetamide,
2- (2-[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-cyclohexyl-N-methylacetamide,
3-chloro-N- {4- [2- (3,4-dihydro-2 (1H) -isoquinolinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2 Methylbenzenesulfonamide,
2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N-phenylacetamide,
2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-isopropyl-N- methylacetamide,
2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-isopropyl-N- methylacetamide,
N-ethyl-N-methyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N- methylacetamide,
N-ethyl-N-methyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-ethyl-N methylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N- methylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N-[(1S) -1-phenylethyl] Acetamide,
3-chloro-2-methyl-N- {4- [2-oxo-2- (l-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2-oxo-2- (l-piperidinyl) ethyl] -1, 3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
N- {4- [2-oxo-2- (l-piperidinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4,6-trichloro-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4, 6-trichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl] -4-sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
2, 4-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4-chloro-2,6-dimethyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-phenoxybenzenesulfonamide,
2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2,4-bis (trifluoromethyl) benzenesulfonamide,
4-bromo-2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4- (2-furyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3'-fluoro-6'-methoxy-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1 ' -Biphenyl] -4-sulfonamide,
4- (5-methyl-2-thienyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3'-acetyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4- Sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4 '-(trifluoromethoxy) [1,1'-ratio Phenyl] -4-sulfonamide,
3 ', 4'-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] 4-sulfonamide,
4- (1,3-benzodioxol-5-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazole-2y1} benzenesulfonamide ,
4- (5-chloro-2-thienyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (4-pyridinyl) benzenesulfonamide,
N- {4 '-[({4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [l, l'- Biphenyl] -3-yl} acetamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (3-thienyl) benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (2-thienyl) benzenesulfonamide,
4 '-[({4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [l, l'-biphenyl] -4-carboxylic acid,
4 '-(methylsulfanyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl ] -4-sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3 ', 5'-bis (trifluoromethyl) [1, l'-biphenyl] -4-sulfonamide,
4'-Chloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4- Sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3'-nitro [1,1'-biphenyl] -4 sulfone amides,
4- (1-benzofuran-2-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (1-pyrrolidinyl) benzenesulfonamide,
4- (4-methyl-1-piperidinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
4-anilino-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4- (benzylamino) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(2-thienylmethyl) amino] benzenesulfonamide,
4- (4-morpholinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4- (4-methyl-1-piperazinyl) -N-{-[2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(3 pyridinylmethyl) amino] benzenesulfonamide,
2,4-dichloro-6-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4 sulfonamide ,
2,4,6-trichloro-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-N- (4- {2- [(2R, 6S) -2,6-dimethylmorpholinyl] -2-oxoethyl} -1,3-thiazol-2-yl) 2-methylbenzene Sulfonamide,
3-Chloro-2-methyl-N- (4- {2-[(1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept-5-yl] -2-oxoethyl} -l , 3-thiazol-2-yl) benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4,6-trichloro-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1, 3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (1,1-dioxido-4-thiomorpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
Tert-butyl 4-[(2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] 1-piperazinecarboxylate,
N- {4- [2- (4-acetyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3-chloro-2-methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluor Low Acetate,
3-chloro-2-methyl-N- {4- [2-oxo-2- (1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluoroacetate,
2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) Benzenesulfonamide,
2, 4-dichloro-6-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
2,4-dichloro-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-N- (4- {2-[(2R) -2,4-dimethylpiperazinyl] -2-oxoethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulphone amides,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methoxy-N- methylacetamide,
3-chloro-2-methyl-N- [4- (2-oxopentyl) -1,3-thiazol-2-yl] benzenesulfonamide,
4-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
3-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- [4- (3-hydroxypropyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-isopropoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
N- {4- [2- (benzyloxy) ethyl] -1,3-thiazol-2-yl} -3-chloro-2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-methoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- {4- [2- (2-fluoroethoxy) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2, 2,2-trifluoroethoxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-pyridinylsulfanyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (3-pyridinyloxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
Methyl 2- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethoxy] benzoate,
3-chloro-N- [5-[(dimethylamino) methyl] -4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl methanesulfonate,
3- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) propyl methanesulfonate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl acetate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl propionate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-methylpropanoate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-furoate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl benzoate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 4-morpholinecarboxylate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) ethyl diethylcarbamate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl ethylcarbamate,
N- [4- (2-azidoethyl) -1, 3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
N- [4- (2-aminoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (methylamino) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
3-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide hydrochloride,
3-chloro-N- {4- [2- (lH-imidazol-1-yl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide dihydrate,
3-chloro-2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide dihydrochloride,
3-chloro-2-methyl-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
3-chloro-2-methyl-N- [4- (4-morpholinylmethyl) -1,3-thiazol-2-yl] benzenesulfonamide hydrochloride,
2,4,6-trichloro-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
2,4-dichloro-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide hydrochloride,
3-chloro-N- {4- [2- (ethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
3-chloro-N- (4- {2-[(2-hydroxyethyl) amino] ethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulfonamide,
3-chloro-N- (4- {3-[(2-hydroxyethyl) amino] propyl} -1,3-thiazol-2-yl) -2 methylbenzenesulfonamide hydrochloride hydrate,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N ethylacetamide,
3-chloro-2-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2 -yl} benzene sulfonamide,
3-chloro-N- {4- [2- (2-hydroxy-3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
2,4-dichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4,6-trichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4,5-dichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-thiophenesulfonamide,
N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -4-phenoxybenzenesulfonamide,
3-fluoro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -5- (2-pyridinyl) -2- thiophensulfonamide,
N- {2-chloro-4-[({4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} amino) sulfonyl] phenyl} acet amides,
3-chloro-2-methyl-N- {4-[(3-oxo-4-morpholinyl) methyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [3- (3-oxo-4-morpholinyl) propyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-N, 2-dimethyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-methyl-3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] acetamide,
3-chloro-2-methyl-N- {4- [2- (3-oxo-1,4-oxazepan-4-yl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-oxo-1-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-oxo-1-imidazolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-oxo-1,3-oxazolidin-3-yl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N- (2-hydroxyethyl) -2 -Furamide,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) ethyl] -N methylcyclopropanecarboxamide,
3-chloro-2-methyl-N- {4- [2- (4-methyl-2-oxo-1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride ,
3-chloro-2-methyl-N- (4- {2-[(methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
3-chloro-2-methyl-N- (4- {2- [methyl (methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
3-chloro-2-methyl-N- [4- (2-{[(trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
3-chloro-2-methyl-N- [4- (2- {methyl [(trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -1methyl-lH-amidazole-4-sulphone amides,
3-chloro-N- (4- {2-[[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] ethyl} -1,3 thiazol-2-yl) -2-methylbenzenesulphone amides,
N- [4- (2-bromoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-chloroethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4-[(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
Ethyl 3- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) propanoate.
[9" claim-type="Currently amended] A compound of formula (II) in the manufacture of a medicament for the prevention, management or treatment of diabetes, syndrome X, obesity, glaucoma, hyperlipidemia, hyperglycemia, hyperinsulinemia, osteoporosis, tuberculosis, dementia, depression, viral disease and inflammatory disorders, or Use of its salts, hydrates or solvates.
Formula II

Wherein T is an aryl ring or heteroaryl ring or aryl-C ₂ -alkenyl ring, optionally independently substituted by [R] n, where n is an integer 0-5 and R is hydrogen, aryl, hetero Aryl, heterocyclic ring, optionally halogenated C _1-6 -alkyl, optionally halogenated C _1-6 -alkoxy, C _1-6 -alkylsulfonyl, carboxy, cyano, nitro, halogen, optionally mono- Or di-substituted amines, optionally mono- or di-substituted amides, aryloxy, arylsulfonyl, arylamino, wherein the aryl, heteroaryl and aryloxy moieties and heterocyclic rings are more optionally at one or more positions independently of each other C _1-6 - acylamino, C _1-6 - alkylthio, cyano, nitro, hydrogen, halogen, optionally halogenated C _l-6-alkyl, optionally halogenated C _1-6 - alkoxy, optionally Mono- or di-substituted amides, (benzoyl No) methyl, carboxy, 2-thienylmethylamino or ({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) Can;
R ¹ is hydrogen or C _1-6 -alkyl;
X is CH ₂ or CO;
Y is CH ₂ , CO or a single bond;
B is hydrogen, C _1-6 -alkyl or dimethylaminomethyl;
R ² is C _1-6 -alkyl, azido, arylthio, heteroarylthio, halogen, hydroxymethyl, 2-hydroxyethylaminomethyl, methylsulfonyloxymethyl, 3-oxo-4-morpholinolinyl Methylene, C _1-6 -alkoxycarbonyl, 5-methyl-1,3,4-oxadiazol-2-yl;
NR ³ R ⁴ , wherein R ³ and R ⁴ are each independently hydrogen, C _1-6 -alkyl, optionally halogenated C _1-6 -alkylsulfonyl, C _1-6 -alkoxy, 2-methoxyethyl, 2 -Hydroxyethyl, 1-methylimidazolylsulfonyl, C _1-6 -acyl, cyclohexylmethyl, cyclopropanecarbonyl, aryl, optionally halogenated arylsulfonyl, furylcarbonyl, tetrahydro-2-furanyl Methyl, N-carbetoxypiperidyl, or C _1-6 -alkyl substituted with one or more aryl or heteroaryl, or
NR ³ R ⁴ is amidazole, piperidine, pyrrolidine, piperazine, morpholine, oxazepine, oxazole, thiomorpholine, 1,1-dioxidothiomorpholine, 2- (3,4- Dihydro-2 (1H) isoquinolinyl), (1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept-5-yl, together with Heterocyclic systems may be optionally substituted by C _1-6 -alkyl, C _1-6 -acyl, hydroxy, oxo, t-butoxycarbonyl;
OCONR ³ R ⁴ , wherein R ³ and R ⁴ are each independently selected from hydrogen, C _1-6 -alkyl or together form morpholinyl;
R ⁵ 0, wherein R ⁵ is hydrogen, optionally halogenated C _1-6 -alkyl, aryl, heteroaryl, C _1-6 -acyl, C _1-6 -alkylsulfonyl, arylcarbonyl, heteroarylcarbonyl, 2-carbomethoxyphenyl.
[10" claim-type="Currently amended] The method of claim 9,
T is 5-chloro-1,3-dimethyl-lH-pyrazol-4-yl; 4-chloro-2,3,1-benzoxadiazolyl; 5- (dimethylamino) -1-naphthyl; 1-methylimidazol-4-yl; 1-naphthyl;
2-naphthyl; (E) -2-phenylethenyl; 8-quinolinyl;
(Benzoylamino) methyl, bromo, chloro, 3-isoxazolyl, 2- (methylsulfanyl) -4-pyrimidinyl, 1-methyl-5- (trifluoromethyl) pyrazol-3-yl, Thienyl substituted with one or more of phenylsulfonyl, pyridyl;
Acetylamino, 3-acetylaminophenyl, 3-acetylphenyl, benzeneamino, 1,3-benzodioxol-5-yl, 2-benzofuryl, benzylamino, 3,5-bis (trifluoromethyl) phenyl, Bromo, butoxy, carboxy, chloro, 4-carboxyphenyl, 3-chloro-2-cyanophenoxy, 4-chlorophenyl, 5-chloro-2-thienyl, cyano, 3,4-dichlorophenyl, ({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl), fluoro, 5-fluoro-2-methoxyphenyl, 2- Furyl, hydrogen, iodo, isopropyl, methanesulfonyl, methoxy, methyl, 4-methyl-l-piperazinyl, 4-methyl-l-piperidinyl, 4-methylsulfanylphenyl, 5-methyl- 2-thienyl, 4-morpholinyl, nitro, 3-nitrophenyl, phenoxy, phenyl, n-propyl, 4-pyridyl, 3-pyridylmethylamino, 1-pyrrolidinyl, 2-thienyl, Substituted with one or more of 3-thienyl, 2-thienylmethylamino, trifluoromethoxy, 4-trifluoromethoxyphenyl, trifluoromethyl Selected from phenyl or; or
R ¹ is hydrogen or methyl;
X is CH ₂ or CO;
Y is CH ₂ , CO or a single bond;
B is hydrogen, methyl or dimethylaminomethyl;
R ² is n-propyl, azido, bromo, chloro, 2-pyridinylsulfanyl, 3-oxo-4-morpholinolinyl methylene, ethoxycarbonyl, 5-methyl-1,3,4-oxa Diazol-2-yl, hydroxymethyl, 2-hydroxyethylaminomethyl, methylsulfonyloxymethyl;
NR ³ R ⁴ , wherein R ³ and R ⁴ are each independently acetyl, benzhydryl, 1,3-benzodioxol-5-ylmethyl, benzyl, 3-chloro-2-methylphenylsulfonyl, cyclohexyl, cyclo Hexylmethyl, cyclopropanecarbonyl, ethyl, 2-furylcarbonyl, 2-furylmethyl, hydrogen, 2-hydroxyethyl, 2- (lH-indol-3-yl) ethyl, isopropyl, methoxy, 2- Methoxyethyl, methyl, 4- (1-methylimidazolyl) sulfonyl, methylsulfonyl, phenyl, (1S) -phenylethyl, n-propyl, tetrahydro-2-furanylmethyl, trifluoromethylsul Fonyl, N-carbetoxypiperidyl; or
NR ³ R ⁴ together are 4-acetylpiperazinyl, 4-t-butoxycarbonylpiperazinyl, 2- (3, 4-dihydro-2 (1H) isoquinolinyl); (2R, 6S) -2, 6-dimethylmorpholinyl, (2R) -2,4-dimethyl-1-piperazinyl, 2-hydroxy-3-oxomorpholinyl, imidazolyl, 2-methyl -3-oxomorpholinyl, 4-methyl-2-oxopiperazinyl, 4-methylpiperazinyl, morpholinyl, (1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept -5-yl, 2-oxoimidazolinyl, 3-oxomorpholinyl, 3-oxo-1, 4-oxazinyl, 2-oxooxazolinyl, piperazinyl; Piperidinyl; Pyrrolidinyl; Pyrrolidoneyl, thiomorpholinyl; 1, 1-dioxido-thiomorpholinyl;
OCONR ³ R ⁴ , wherein R ³ and R ⁴ are each independently selected from ethyl, hydrogen or together form morpholinyl;
R ⁵ 0, where R ⁵ is acetyl, benzoyl, benzyl, ethyl, 2-fluoroethyl, 2-furylcarbonyl, hydrogen, isobutyryl, isopropyl, methyl, 2-carbomethoxyphenyl, methylsulfonyl, Phenyl, propionyl, 3-pyridinyl, 2,2,2-trifluoroethyl.
[11" claim-type="Currently amended] Use according to claim 9 or 10, characterized in that the compound is selected from:
: Ethyl (2-{[(2,4-dichloro-5-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-[[(4-chlorophenyl) sulfonyl] amino] -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-{[(4-chloro-2,5-dimethylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2- {[(2,4-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-(((4-methylphenyl) sulfonyl) amino) -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-{[(2, 5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl 2- (2-{[(3-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-[(3-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-[(phenylsulfonyl) amino] -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-isopropylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[3-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino)- 1,3-thiazol-4-yl] acetate,
Ethyl [2-({[4-({[4- (2-ethoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} carbonyl) phenyl] sulfonyl} amino)- 1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[2- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-({[3- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-({[4- (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl 2- (2-{[(4-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-[(2-nitrophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2, 4, 6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(5-fluoro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-methoxy-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3,5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(3,4-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-butoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (acetylamino) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl {2-[(8-quinolinylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl (2-{[(3,4-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-iodophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-chloro-4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[5- (dimethylamino) -1-naphthyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[1-methyl-1H-imidazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(5-bromo-2-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2- {[(2, 5-dimethoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
ethyl. {2-[(2-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl {2-[(methylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl (2-{[(3-bromo-5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl {2-[({5-[(benzoylamino) methyl] -2-thienyl} sulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl {2-[({5- [l-methyl-5- (trifluoromethyl) -lH-pyrazol-3-yl] -2- thienyl} sulfonyl) amino] -1,3-thiazole -4-yl} acetate,
Ethyl (2-{[(4-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl {2-[({5- (2-methylsulfanyl) -4-pyrimidinyl] -2-thienyl} sulfonyl) amino] -1,3thiazol-4-yl} acetate,
Ethyl (2-{[(3-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4,5-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[(E) -2-phenylethenyl] sulfonyl] amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2,3,4-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-bromo-2, 5-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2, 3-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-bromophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4,5-dichloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-({[5- (phenylsulfonyl) -2-thienyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(2,6-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-cyanophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (acetylamino) -3-chlorophenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(5-chloro-1,3-dimethyl-lH-pyrazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-methoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-bromo-5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl 2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl (2-{[(2, 5-dichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[4- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-{[2- (methylsulfonyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl (2-{[(4-bromo-2-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,3,4-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(7-chloro-2,1,3-benzoxadiazol-4-yl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2,4,6-trifluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
2-chloro-5-({4- (2-methoxy-2-oxoethyl) -1,3-thiazol-2-yl] amino} sulfonyl) -4-fluorobenzoic acid,
Ethyl (2-{[(5-chloro-2-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(2-chloro-4-fluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[5- (3-isoxazolyl) -2-thienyl] sulfonyl} amino) -1, 3-thiazol-4-yl] acetate,
Ethyl (2-{[(4-bromo-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(4-phenoxyphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[4-chloro-2, 6-dimethylphenyl) sulfonyl amino} -1,3-thiazol-4-yl) acetate,
Ethyl [2-({[2-methyl-4- (trifluoromethoxy) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl [2-(([2,4-bis (trifluoromethyl) phenyl] sulfonyl} amino) -1,3-thiazol-4-yl] acetate,
Ethyl 2- {2-[[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] -1,3-thiazol-4-yl} acetate,
Ethyl oxo (2-[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) (oxo) acetate,
Ethyl oxo (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Ethyl {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} (oxo) acetate,
Ethyl (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) (oxo) acetate,
2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
2- (2-{[(2,5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
(2-{[(2-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetic acid,
Isopropyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Phenyl 2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl 2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -5-methyl-1,3-thiazol-4-yl} acetate,
Methyl (2-{[(4-chlorophenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
Methyl (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
Methyl [2-({[4- (3-chloro-2-cyanophenoxy) phenyl] sulfonyl} amino) -5-methyl-1,3-thiazol-4-yl] acetate,
Methyl (5-methyl-2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl (5-methyl-2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetate,
Methyl (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -5-methyl-1,3-thiazol-4-yl) acetate,
N- (2-methoxyethyl) -2- (2-{[(4-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(2, 5-dichloro-3-thienyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
N- (1,3-benzodioxol-5-ylmethyl) -2- {2- [(l-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
N- (2-furylmethyl) -2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
2- (2-{[(2,4-difluorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
N-isopropyl-2- {2-[(1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
N- [2- (1H-indol-3-yl) ethyl] -2- {2- [1-naphthylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
N- (cyclohexylmethyl) -2- {2-[(phenylsulfonyl) amino] -1,3-thiazol-4-yl} acetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide,
2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N- (2furylmethyl) acetamide,
N-benzhydryl-2- (2- {[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N- (tetrahydro-2furanylmethyl) acetamide,
Ethyl 4-{[2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] amino} -1 piperidinecarboxylate,
N-benzhydryl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(4-chlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-phenylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diethylacetamide,
2- {2- [([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diethylacetamide,
N, N-diethyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diethylacetamide,
N, N-diethyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- {2-[([1-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N, N-diisopropylacetamide,
N, N-diisopropyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2- {[(2, 4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N- diisopropylacetamide,
N, N-diisopropyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl amino} -1,3-thiazol-4-yl) acetamide,
2- (2-[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-diisopropylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dipropylacetamide,
N-benzyl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methylacetamide,
N-benzyl-2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N ethylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N, N-dimethylacetamide,
2- (2-[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-cyclohexyl-N-methylacetamide,
3-chloro-N- {4- [2- (3,4-dihydro-2 (1H) -isoquinolinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2 Methylbenzenesulfonamide,
2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N-phenylacetamide,
2- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-isopropyl-N- methylacetamide,
2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-isopropyl-N- methylacetamide,
N-ethyl-N-methyl-2- (2-{[(2,4,6-trichlorophenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- (2-{[(2,4-dichloro-6-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N- methylacetamide,
N-ethyl-N-methyl-2- (2-{[(4-propylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetamide,
2- {2-[([1,1'-biphenyl] -4-ylsulfonyl) amino] -1,3-thiazol-4-yl} -N-ethyl-N methylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-ethyl-N- methylacetamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methyl-N-[(1S) -1-phenylethyl] Acetamide,
3-chloro-2-methyl-N- {4- [2-oxo-2- (l-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2-oxo-2- (l-piperidinyl) ethyl] -1, 3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
N- {4- [2-oxo-2- (l-piperidinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4,6-trichloro-N- {4- [2-oxo-2- (1-piperidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4, 6-trichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl] -4-sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
2, 4-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4-chloro-2, 6-dimethyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4 phenoxybenzenesulfonamide,
2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -2,4-bis (trifluoromethyl) benzenesulfonamide,
4-bromo-2-methyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4- (2-furyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3'-fluoro-6'-methoxy-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1 ' -Biphenyl] -4-sulfonamide,
4- (5-methyl-2-thienyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3'-acetyl-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4- Sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4 '-(trifluoromethoxy) [1,1'-ratio Phenyl] -4-sulfonamide,
3 ', 4'-dichloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] 4-sulfonamide,
4- (1,3-benzodioxol-5-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazole-2y1} benzenesulfonamide ,
4- (5-chloro-2-thienyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (4-pyridinyl) benzenesulfonamide,
N- {4 '-[({4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [l, l'- Biphenyl] -3-yl} acetamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (3-thienyl) benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (2-thienyl) benzenesulfonamide,
4 '-[({4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} amino) sulfonyl] [l, l'-biphenyl] -4-carboxylic acid,
4 '-(methylsulfanyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [l, l'-biphenyl ] -4-sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3 ', 5'-bis (trifluoromethyl) [1, l'-biphenyl] -4-sulfonamide,
4'-Chloro-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4- Sulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3'-nitro [1,1'-biphenyl] -4 sulfone amides,
4- (1-benzofuran-2-yl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (1-pyrrolidinyl) benzenesulfonamide,
4- (4-methyl-1-piperidinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
4-anilino-N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4- (benzylamino) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(2-thienylmethyl) amino] benzenesulfonamide,
4- (4-morpholinyl) -N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4- (4-methyl-1-piperazinyl) -N-{-[2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-[(3 pyridinylmethyl) amino] benzenesulfonamide,
2,4-dichloro-6-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4 sulfonamide ,
2,4,6-trichloro-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {5-methyl-4- [2- (4-morpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-N- (4- {2- [(2R, 6S) -2,6-dimethylmorpholinyl] -2-oxoethyl} -1,3-thiazol-2-yl) 2-methylbenzene Sulfonamide,
3-Chloro-2-methyl-N- (4- {2-[(1S, 4S) -2-oxa-5-azabicyclo [2.2.1] hept-5-yl] -2-oxoethyl} -l , 3-thiazol-2-yl) benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} [1,1'-biphenyl] -4-sulfonamide,
N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4,6-trichloro-N- {4- [2-oxo-2- (4-thiomorpholinyl) ethyl] -1, 3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (1,1-dioxido-4-thiomorpholinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide,
Tert-butyl 4-[(2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) acetyl] 1-piperazinecarboxylate,
N- {4- [2- (4-acetyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -3-chloro-2-methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluor Low Acetate,
3-chloro-2-methyl-N- {4- [2-oxo-2- (1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide trifluoroacetate,
2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} -4- (trifluoromethoxy) Benzenesulfonamide,
2, 4-dichloro-6-methyl-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
2,4-dichloro-N- {4- [2- (4-methyl-1-piperazinyl) -2-oxoethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-N- (4- {2-[(2R) -2,4-dimethylpiperazinyl] -2-oxoethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulphone amides,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) -N-methoxy-N- methylacetamide,
3-chloro-2-methyl-N- [4- (2-oxopentyl) -1,3-thiazol-2-yl] benzenesulfonamide,
4-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
3-chloro-N- [4- (2-hydroxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- [4- (3-hydroxypropyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-isopropoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
N- {4- [2- (benzyloxy) ethyl] -1,3-thiazol-2-yl} -3-chloro-2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-methoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-N- {4- [2- (2-fluoroethoxy) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2, 2,2-trifluoroethoxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-pyridinylsulfanyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (3-pyridinyloxy) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
Methyl 2- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethoxy] benzoate,
3-chloro-N- [5-[(dimethylamino) methyl] -4- (2-ethoxyethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl methanesulfonate,
3- (2- {[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) propyl methanesulfonate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl acetate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl propionate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-methylpropanoate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 2-furoate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl benzoate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl 4-morpholinecarboxylate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) ethyl diethylcarbamate,
2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl ethylcarbamate,
N- [4- (2-azidoethyl) -1, 3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
N- [4- (2-aminoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (methylamino) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
3-chloro-N- {4- [2- (diethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide hydrochloride,
3-chloro-N- {4- [2- (lH-imidazol-1-yl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide dihydrate,
3-chloro-2-methyl-N- {4- [2- (4-methyl-1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide dihydrochloride,
3-chloro-2-methyl-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
3-chloro-2-methyl-N- [4- (4-morpholinylmethyl) -1,3-thiazol-2-yl] benzenesulfonamide hydrochloride,
2,4,6-trichloro-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
2,4-dichloro-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
2,4-dichloro-6-methyl-N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride,
N- {4- [2- (4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -4-propylbenzenesulfonamide hydrochloride,
3-chloro-N- {4- [2- (ethylamino) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
3-chloro-N- (4- {2-[(2-hydroxyethyl) amino] ethyl} -1,3-thiazol-2-yl) -2-methylbenzenesulfonamide,
3-chloro-N- (4- {3-[(2-hydroxyethyl) amino] propyl} -1,3-thiazol-2-yl) -2 methylbenzenesulfonamide hydrochloride hydrate,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N ethylacetamide,
3-chloro-2-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2 -yl} benzene sulfonamide,
3-chloro-N- {4- [2- (2-hydroxy-3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-methylbenzenesulfonamide,
2,4-dichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4-dichloro-6-methyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
2,4,6-trichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
4,5-dichloro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -2-thiophenesulfonamide,
N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -4-phenoxybenzenesulfonamide,
3-fluoro-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} -5- (2-pyridinyl) -2- thiophensulfonamide,
N- {2-chloro-4-[({4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} amino) sulfonyl] phenyl} acet amides,
3-chloro-2-methyl-N- {4-[(3-oxo-4-morpholinyl) methyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [3- (3-oxo-4-morpholinyl) propyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-N, 2-dimethyl-N- {4- [2- (3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-methyl-3-oxo-4-morpholinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] acetamide,
3-chloro-2-methyl-N- {4- [2- (3-oxo-1,4-oxazepan-4-yl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-oxo-1-pyrrolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-oxo-1-imidazolidinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide,
3-chloro-2-methyl-N- {4- [2- (2-oxo-1,3-oxazolidin-3-yl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -N- (2-hydroxyethyl) -2 -Furamide,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino) -1,3-thiazol-4-yl) ethyl] -N methylcyclopropanecarboxamide,
3-chloro-2-methyl-N- {4- [2- (4-methyl-2-oxo-1-piperazinyl) ethyl] -1,3-thiazol-2-yl} benzenesulfonamide hydrochloride ,
3-chloro-2-methyl-N- (4- {2-[(methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
3-chloro-2-methyl-N- (4- {2- [methyl (methylsulfonyl) amino] ethyl} -1,3-thiazol-2-yl) benzenesulfonamide,
3-chloro-2-methyl-N- [4- (2-{[(trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
3-chloro-2-methyl-N- [4- (2- {methyl [(trifluoromethyl) sulfonyl] amino} ethyl) -1,3-thiazol-2-yl] benzenesulfonamide,
N- [2- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) ethyl] -1methyl-lH-amidazole-4-sulphone amides,
3-chloro-N- (4- {2-[[(3-chloro-2-methylphenyl) sulfonyl] (methyl) amino] ethyl} -1,3 thiazol-2-yl) -2-methylbenzenesulphone amides,
N- [4- (2-bromoethyl) -1,3-thiazol-2-yl] -3-chloro-2-methylbenzenesulfonamide,
3-chloro-N- [4- (2-chloroethyl) -1,3-thiazol-2-yl] -2-methylbenzenesulfonamide,
3-chloro-2-methyl-N- {4-[(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1,3-thiazol-2-yl} benzenesulfonamide ,
Ethyl 3- (2-{[(3-chloro-2-methylphenyl) sulfonyl] amino} -1,3-thiazol-4-yl) propanoate.
[12" claim-type="Currently amended] A pharmaceutical composition comprising one or more compounds of formula (II) as defined in any one of claims 9 to 11 and a pharmaceutically acceptable carrier.

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AU6093101A|2001-12-03|

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EP1283834B1|2009-09-16|

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ES2333846T3|2010-03-02|

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HU0302435A3|2007-05-02|

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EP1283831A1|2003-02-19|

引用文献:

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公开号 | 申请日 | 公开日 | 申请人 | 专利标题

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法律状态:
2000-05-22|Priority to SE0001899A

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2000-05-22|Priority to SE0001899-4

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2001-05-22|Application filed by 바이오비트럼 에이비

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2003-02-26|Publication of KR20030016269A

优先权:

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申请号 | 申请日 | 专利标题

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SE0001899A|SE0001899D0|2000-05-22|2000-05-22|New compounds|

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SE0001899-4|2000-05-22|